Inhibition of the JAK-STAT3 Pathway by Andrographolide Enhances Chemo-Sensitivity of Cancer Cells to Doxorubicin

Biochem Pharmacol. 2009 Dec 17. [Epub ahead of print]

Inhibition of the JAK-STAT3 Pathway by Andrographolide Enhances
Chemo-Sensitivity of Cancer Cells to Doxorubicin.

Zhou J, Ong CN, Hur GM, Shen HM.

Department of Epidemiology and Public Health, Yong Loo Lin School of
Medicine, Republic of Korea.

Andrographolide (Andro), a diterpenoid lactone isolated from a
traditional herbal medicine Andrographis paniculata, is known to
possess potent anti-inflammatory and anticancer property. In this
study, we sought to examine the effect of Andro on Signal Transducer
and Activator of Transcription 3 (STAT3) pathway and evaluate whether
suppression of STAT3 activity by Andro could sensitize cancer cells to
a chemotherapeutic drug doxorubicin. First, we demonstrated that Andro
is able to significantly suppress both constitutively activated and
IL-6-induced STAT3 phosphorylation and subsequent nuclear
translocation in cancer cells. Such inhibition is found to be achieved
through suppression of Janus-activated kinase (JAK)1/2 and interaction
between STAT3 and gp130. For understanding the biological significance
of the inhibitory effect of Andro on STAT3, we next investigated the
effect of Andro on doxorubicin-induced apoptosis in human cancer
cells. In our study the constitutive activation level of STAT3 was
found to be correlated to the resistance of cancer cells to
doxorubicin-induced apoptosis. Both the short-term MTT assay and the
long-term colony formation assay showed that Andro dramatically
promoted doxorubicin-induced cell death in cancer cells, indicating
that Andro enhances the sensitivity of cancer cells to doxorubicin
mainly via STAT3 suppression. These observations thus reveal a novel
anti-cancer function of Andro and suggest a potential therapeutic
strategy of using Andro in combination with chemotherapeutic agents
for treatment of cancer. Copyright © 2009. Published by Elsevier Inc.

PMID: 20026083 [PubMed - as supplied by publisher]

Efficacy of botanical extracts against Japanese encephalitis vector, Culex tritaeniorhynchus

Parasitol Res. 2009 Dec 2. [Epub ahead of print]

Efficacy of botanical extracts against Japanese encephalitis vector, Culex tritaeniorhynchus.

Elango G, Rahuman AA, Bagavan A, Kamaraj C, Zahir AA, Rajakumar G, Marimuthu S, Santhoshkumar T.

Unit of Bioactive Natural Products, Post Graduate and Research Department of Zoology, C. Abdul Hakeem College, Melvisharam, 632 509, Vellore District, Tamil Nadu, India.

The purpose of the present study was to assess the effect of leaf hexane and chloroform extracts of Aegle marmelos, Andrographis lineata, Andrographis paniculata, Cocculus hirsutus, Eclipta prostrata, and Tagetes erecta on repellent, ovicidal, and oviposition-deterrent activities against Culex tritaeniorhynchus Giles (Diptera: Culicidae). The repellent action of the plant extracts tested varied depending on the plant species, part, solvent used in extraction, and the extract dose. The hexane extract of A. paniculata was more effective in exhibiting the repellent action against the mosquito as compared with A. lineata extract. Complete protections for 150 min were found in hexane extract of A. paniculata at 500 ppm against mosquito bites. Mean percent hatchability of the ovicidal activity was observed 24 h after treatment. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. No hatchability was observed with hexane, and chloroform extracts of A. lineata, A. paniculata, and hexane extract of T. erecta were exerted at 1,000 ppm. The percentage of effective oviposition repellency were 95.90, 94.75, 95.04, 90.58, 87.93, 87.14, 94.82, 95.71, 92.26, 90.58, 83.35, and 78.16 at 500 ppm, and the lowest repellency was 69.93, 53.06, 64.81, 70.06, 51.82, 54.54, 48.31, 66.71, 68.82, 61.85, 34.84, and 39.53 at 31.25 ppm in hexane and chloroform extracts of A. marmelos, A. lineata, A. paniculata, C. hirsutus, E. prostrata, and T. erecta, respectively. The oviposition activity index values revealed that the solvent plant extracts have deterrent effect, and they caused a remarkable negative response resulting in oviposition of very few eggs. These results clearly reveal that the hexane extracts of A. marmelos and A. paniculata served as a potential repellent, ovicidal, and oviposition deterrent against Japanese encephalitis vector, C. tritaeniorhynchus.

PMID: 19953270 [PubMed - as supplied by publisher]

Chemical Fingerprinting of Andrographis paniculata (Burm. f.) Nees by HPLC and Hierarchical Clustering Analysis

J Chromatogr Sci. 2009 Nov-Dec;47(10):931-5.

Chemical Fingerprinting of Andrographis paniculata (Burm. f.) Nees by
HPLC and Hierarchical Clustering Analysis.

Dong HJ, Zhang ZJ, Yu J, Liu Y, Xu FG.

Key laboratory of Drug Quality Control and Pharmacovigilance (China
Pharmaceutical University), Ministry of Education, Nanjing
210009,China; Center for Instrumental Analysis, China Pharmaceutical
University, Nanjing 210009, China.

The aim is to develop a simple and specific method for the extraction
and chemical fingerprinting of Andrographis paniculata (Burm. f.) Nees
and to apply the method to this drug from different regions.
High-performance liquid chromatographic (HPLC) with gradient elution
is used for developing the fingerprints, and liquid chromatography
electrospray ionization mass spectrometry (LC-ESI-MS) technique is
employed to identify the component of the fingerprints. Nine peaks are
selected as common peaks, and six compounds are elucidated by MS data.
Twenty-three samples of A. paniculata from different regions of China
are collected and detected by HPLC fingerprinting. Comparisons of the
chromatograms show that there are obvious differences in the content
of each component contained between the habitat samples in China. The
results of hierarchical cluster analysis show that these samples can
be clustered reasonably into three groups, and the growth of A.
paniculata and their internal quality are related to their habitat.
The HPLC fingerprint developed allows simple identification of A.
paniculata from many natural drugs.

PMID: 19930808 [PubMed - in process]

The effect of Eurycoma longifolia on sperm quality of male rats

Nat Prod Commun. 2009 Oct;4(10):1331-6.

The effect of Eurycoma longifolia on sperm quality of male rats.

Chan KL, Low BS, Teh CH, Das PK.

School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800
Penang, Malaysia. klchan@usm.my

The present study investigated the effects of a standardized methanol
extract of E. longifolia Jack containing the major quassinoid
constituents of 13alpha(21)-epoxyeurycomanone (1), eurycomanone (2),
13alpha,21-dihydroeurycomanone (3) and eurycomanol (4) on the
epididymal spermatozoa profile of normal and Andrographis paniculata
induced infertile rats. The standardized MeOH extract at doses of 50,
100 and 200 mg/kg, the EtOAc fraction (70 mg/kg), and standardized
MeOH extract at 200 mg/kg co-administered with the EtOAc fraction of
A. paniculata at 70 mg/kg were each given orally to male
Sprague-Dawley albino rats for 48 consecutive days. The spermatozoa
count, morphology, motility, plasma testosterone level and Leydig cell
count of the animals were statistically analyzed by ANOVA with a
post-hoc Tukey HSD test. The results showed that the sperm count of
rats given the standardized MeOH extract alone at doses of 50, 100 and
200 mg/kg were increased by 78.9, 94.3 and 99.2%, respectively when
compared with that of control (p < 0.01). The low count, poor motility
and abnormal morphology of the spermatozoa induced by the A.
paniculata fraction were significantly reversed by the standardized
MeOH extract of E. longifolia (p < 0.001). The plasma testosterone
level of the rats treated with the standardized MeOH extract at 200
mg/kg was significantly increased (p < 0.01) when compared with that
of the control and infertile animals. The spermatocytes in the
seminiferous tubules and the Leydig cells appeared normal.
Testosterone level was significantly higher in the testes (p < 0.01)
than in the plasma after 30 days of oral treatment with the
standardized MeOH extract. Interestingly, eurycomanone (2) alone was
detected in the rat testis homogenates by HPLC-UV and confirmed by
LC/MS, and may have contributed towards the improvement of sperm
quality. Thus, the plant may potentially be suitable for the
management of male infertility.

PMID: 19911566 [PubMed - in process]

Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis

Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G₁ arrest and apoptosis

S R Jada, C Matthews, M S Saad, A S Hamzah, N H Lajis, M F G Stevens, and J Stanslas

Br J Pharmacol. 2008 November; 155(5): 641–654. Published online 2008 September 22. doi: 10.1038/bjp.2008.368.

Background and purpose:
Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.

Experimental approach:
Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.

Key results:
Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G1 arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis.

Conclusion and implications:
The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G1 phase cell cycle arrest, coupled with induction of apoptosis.

Keywords: andrographolide derivatives, antitumour, cell cycle, G1 arrest, NCI cell lines, CDK-4, apoptosis, v-Src

PMCID: PMC2584933

| Abstract | Full Text | PDF–428K |

Evaluation of immunomodulatory activity of an extract of andrographolides from Andographis paniculata

Planta Med. 2009 Jun;75(8):785-91. Epub 2009 Mar 4.

Evaluation of immunomodulatory activity of an extract of
andrographolides from Andographis paniculata.

Naik SR, Hule A.

Prin. K. M. Kundnani College of Pharmacy, Rambhau Salgaonkar Marg,
Cuff, Parade, Colaba, Mumbai, India. srnaik5@rediffmail.com

The immunomodulatory activity of HN-02, an extract containing a
mixture of andrographolides (i.e., andrographolide [88 +/- 5 %] plus
14-deoxyandrographolide and 14-deoxy-11,12-didehydroandrographolide
together [12 +/- 3 %]) in a pure powder form was evaluated at 1.0,
1.5, and 2.5 mg/kg on different in vivo and in vitro experimental
models. In a delayed-type hypersensitivity (DTH) mouse model,
potentiation of the DTH reaction was observed after treatment with
cyclophosphamide (CYP) and HN-02 individually. However, CYP
potentiation of the DTH reaction was reversed by HN-02 pretreatment.
Furthermore, HN-02 treatment elevated the depressed hemagglutination
antibody (HA) titer and increased the number of plaque-forming cells
(PFCs) in the spleen cells of mice that had been treated with CYP and
challenged with sheep red blood cells (SRBC). Further, it was also
found that HN-02 treatment stimulated phagocytosis in mice. A
significant increase in total WBC count and relative weight of spleen
and thymus was observed in mice during 30 days of treatment with
HN-02. The present experimental findings demonstrate that HN-02 has
the ability to enhance immune function, possibly through modulation of
immune responses altered during antigen interaction, and to reverse
the immunosuppression induced by CYP.

PMID: 19263340 [PubMed - indexed for MEDLINE]

Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals

Arch Pharm Res. 2009 Sep;32(9):1191-200. Epub 2009 Sep 26.

Analgesic, antipyretic, anti-inflammatory and toxic effects of
andrographolide derivatives in experimental animals.

Suebsasana S, Pongnaratorn P, Sattayasai J, Arkaravichien T, Tiamkao
S, Aromdee C.

Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon
Kaen University, Khon Kaen, Thailand.

Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2)
are active constituents of Andrographis paniculata (Burm. f.), family
Acanthaceae. A. paniculata extracts are reported to have antiviral,
antipyretic, immunostimulant and anticancer activities. In this study,
1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as
well as 2 and its 3,19-dipalmitoyl-derivative (5), were
intraperitoneally tested for their analgesic, antipyretic,
anti-inflammatory and acute toxicity effects in animal models.
Analgesic effects were tested in mice using hot plate and writhing
tests to distinguish the central and peripheral effects, respectively.
The results showed that, at 4 mg/kg, all tested substances have
significant analgesic effects, and the highest potency was seen with
3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase
the analgesic effect. In the writhing test, 3 and 5, but not 1, showed
significant results. In a baker's yeast-induced fever model, 3 and 5
significantly reduced rats' rectal temperature (p < 0.05). In a
carrageenan-induced inflammation model, 1, 3 and 5 significantly
reduced rats' paw volume. Doses of 3 and 5 up to 100 mg/kg did not
show any serious toxic effects. From this study, 3 and 5 are the most
interesting derivatives, showing much greater potency than their
parent compounds. These could be further developed as analgesic,
antipyretic and anti-inflammatory agents, without any serious
toxicity.

PMID: 19784573 [PubMed - in process]

Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon

Evid Based Complement Alternat Med. 2009 Sep 14. [Epub ahead of print]

Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon.

Varma A, Padh H, Shrivastava N.

B. V. Patel Pharmaceutical Education & Research Development (PERD)
Centre, Sarkhej-Gandhinagar Highway, Thaltej, Ahmedabad 380054,
Gujarat, India. neetashrivastava_perd@yahoo.co.in.

Plant-derived natural products occupy an important position in the
area of cancer chemotherapy. Molecules such as vincristine,
vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin,
etc. are invaluable contributions of nature to modern medicine.
However, the quest to find out novel therapeutic compounds for cancer
treatment and management is a never-ending venture; and diverse plant
species are persistently being studied for identification of
prospective anticancer agents. In this regard, Andrographis paniculata
Nees, a well-known plant of Indian and Chinese traditional system of
medicines, has drawn attention of researchers in recent times.
Andrographolide, the principal bioactive chemical constituent of the
plant has shown credible anticancer potential in various
investigations around the globe. In vitro studies demonstrate the
capability of the compound of inducing cell-cycle arrest and apoptosis
in a variety of cancer cells at different concentrations.
Andrographolide also shows potent immunomodulatory and anti-angiogenic
activities in tumorous tissues. Synthetic analogues of the compound
have also been created and analyzed, which have also shown similar
activities. Although it is too early to predict its future in cancer
chemotherapy, the prologue strongly recommends further research on
this molecule to assess its potential as a prospective anticancer
agent.

PMID: 19752167 [PubMed - as supplied by publisher]

Inhibitory effects of ethyl acetate extract of Andrographis paniculata on NF-{kappa}B trans-activation activity and LPS-induced acute inflammation in mice

Evid Based Complement Alternat Med. 2009 Sep 10. [Epub ahead of print]

Inhibitory effects of ethyl acetate extract of Andrographis paniculata
on NF-{kappa}B trans-activation activity and LPS-induced acute
inflammation in mice

Chao WW, Kuo YH, Hsieh SL, Lin BF.

Department of Biochemical Science and Technology, Institute of
Microbiology and Biochemistry, College of Life Science, National
Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617,
Taipei, Taiwan, ROC. bifong@ntu.edu.tw.

This study was to investigate anti-inflammatory effect of Andrographis
paniculata (Burm. f.) Nees (Acanthaceae) (AP). The effects of ethyl
acetate (EtOAc) extract from AP on the level of inflammatory mediators
were examined first using nuclear factor kappa B (NF-kappaB) driven
luciferase assay. The results showed that AP significantly inhibited
NF-kappaB luciferase activity and tumor necrosis factor alpha
(TNF-alpha), interleukin 6 (IL-6), macrophage inflammatory protein-2
(MIP-2) and nitric oxide (NO) secretions from lipopolysaccharide
(LPS)/interferon-gamma stimulated Raw264.7 cells. To further evaluate
the anti-inflammatory effects of AP in vivo, BALB/c mice were tube-fed
with 0.78 (AP1), 1.56 (AP2), 3.12 (AP3) and 6.25 (AP4) mg kg(-1) body
weight (BW)/day in soybean oil, while the control and PDTC
(pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were
tube-fed with soybean oil only. After 1 week of tube-feeding, the PDTC
group was injected with 50 mg kg(-1) BW PDTC and 1 h later, all of the
mice were injected with 15 mg kg(-1) BW LPS. The results showed that
the AP1, AP2, AP3 and PDTC groups, but not AP4, had significantly
higher survival rate than the control group. Thus, the control, AP1,
AP2, AP3 and PDTC groups were repeated for in vivo parameters. The
results showed that the AP and PDTC groups had significantly lower
TNF-alpha, IL-12p40, MIP-2 or NO in serum or peritoneal macrophages
and infiltration of inflammatory cells into the lung of mice. The AP1
group also had significantly lower MIP-2 mRNA expression in brain.
This study suggests that AP can inhibit the production of inflammatory
mediators and alleviate acute hazards at its optimal dosages.

PMID: 19745004 [PubMed - as supplied by publisher]

Synergistic increases of metabolism and oxidation-reduction genes on their expression after combined treatment with a CYP1A inducer and andrographolide

Chem Biol Interact. 2009 Sep 5. [Epub ahead of print]

Synergistic increases of metabolism and oxidation-reduction genes on
their expression after combined treatment with a CYP1A inducer and
andrographolide

Chatuphonprasert W, Jarukamjorn K, Kondo S, Nemoto N.

Department of Toxicology, Graduate School of Medicine and
Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama
930-0194 Japan; Academic Office for Pharmaceutical Sciences, Faculty
of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002
Thailand.

We previously reported that andrographolide greatly enhanced the
expression of CYP1A1. Since andrographolide is a major constituent of
Andrographis paniculata, which has been employed for centuries in Asia
and Europe as a folk remedy, we further analyzed genes whose
expression was modified by andrographolide using primary-cultured
mouse hepatocytes in a microarray assay. With the threshold for
modification set at 2-fold, andrographolide up-regulated 18 genes
among 28,853 genes, most of them related to
metabolism/oxidation/reduction. Meanwhile, 5 genes, related to protein
binding or calcium ion binding, were down-regulated. A combination of
beta-naphthoflavone (beta-NF), a CYP1A inducer, and andrographolide
modified the expression of 45 genes (27 up-regulated and 18
down-regulated), although beta-NF single treatment up-regulated 4
genes. The affected genes were again mostly related to metabolism and
oxidation-reduction. Among P450 isoforms, andrographolide by itself
induced CYP1A1, CYP2A4, CYP2B9, and CYP2B10 expression. Synergistic
expression of CYP1A1 and CYP1B1 mRNA was confirmed by quantitative
RT-PCR. These observations suggest that drug interaction and risk
assessment with the use of andrographolide or A. paniculata should be
elucidated.

PMID: 19737545 [PubMed - as supplied by publisher]

Renoprotective effects of Andrographis paniculata (Burm. f.) Nees in rats

Ups J Med Sci. 2009;114(3):136-9.

Singh P, Srivastava MM, Khemani LD.

Department of Chemistry, Dayalbagh Educational Institute (Deemed
University), Agra, India.

Background. Renal failure is an increasingly common condition with
limited treatment options that is causing a major financial and
emotional burden on the community. Andrographis paniculata is the
plant used in Ayurveda for several remedies. Scientific evidence
suggests its versatile biological functions that support its
traditional use in the Orient. The plant is claimed to possess
immunological, antibacterial, anti-inflammatory, antithrombotic, and
hepatoprotective properties. But, to date, there is no study
demonstrating the protective effect of A. paniculata on
gentamicin-induced renal failure. The present study aims to highlight
the first ever reported, antirenal failure activity of A. paniculata.
Methods. Male Wistar albino rats were divided into three groups:
normal control, gentamicin control, and aqueous extract of A.
paniculata (200 mg/kg, per oral (p.o.))-treated. The nephrotoxic model
was induced by gentamicin (80 mg/kg, intraperitoeal (i.p.)). Blood
samples were examined for serum creatinine, serum urea, and blood urea
nitrogen after the 10 days of treatment. Results. A gentamicin-induced
nephrotoxic animal model was successfully prepared. Aqueous extract of
A. paniculata attenuated the gentamicin-induced increase in serum
creatinine, serum urea, and blood urea nitrogen levels by 176.92%,
106.27%, and 202.90%, respectively. Conclusion. The present study
reports that the aqueous extract (whole plant) of A. paniculata (Burm.
f.) Nees exhibits a significant renoprotective effect in
gentamicin-induced nephrotoxicity in male Wistar albino rats.

PMID: 19736602 [PubMed - in process]

Potency of andrographolide as an antitumor compound in BHC-induced liver damage

Integr Cancer Ther. 2009 Jun;8(2):177-89.Related Articles, LinkOut

Trivedi NP, Rawal UM, Patel BP.

Department of Zoology, School of Sciences, Gujarat University, India.

RELEVANCE: The present investigation relates to the influence of
andrographolide, an active compound of Andrographis paniculata Nees.
It reverses an experimental liver carcinogenic condition of mice to
normal and might be a potential therapeutic/preventive agent for human
liver cancer. OBJECTIVE: A. paniculata (Kalmegh) is extensively used
in the Indian traditional system of medicine as a hepatoprotective and
hepatostimulative agent and has been reported to have protective
effect against different hepatotoxins. MATERIALS AND METHODS:
Histomorphological, ultrastructural, and biochemical studies were
performed for the effect of the andrographolide on control mice, mice
treated with hexachlorocyclohexane (BHC) only and BHC +
andrographolide. Enzymes for liver function tests were analyzed by
spectrophotometric method. RESULTS: The BHC experimental model forms
an irreversible liver tumor in male mice. The histological and
ultrastructural changes observed in andrographolide supplementation
emphasize the recovery of the damaged liver. This recovery was also
reflected in the neoplastic nodule formation. The activity of
phosphorylase and glucose-6-phosphatase in the liver of the
andrographolide-supplemented group suggests improved glycogenolysis in
liver. Serum glutamate pyruvate transaminase, serum glutamate oxalate
transaminase, alkaline phosphatase, acid phosphatase, and
gamma-glutamyl transpeptidase showed a significant decrease in
andrographolide-supplemented animals as compared with BHC-treated
animals, suggesting regenerative effects elicited by andrographolide.
CONCLUSION: The study indicates that the regenerative capability
elicited by andrographolide is possibly due to its ability to
reactivate liver function enzymes that catalyze the reaction of
several biochemical and synthetic processes and that it may be useful
for severe liver damage conditions.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 19679627 [PubMed - in process]

Antinociceptive and Antiedematogenic Activities of Andrographolide Isolated From Andrographis paniculata in Animal Models

Biol Res Nurs. 2009 Aug 18. [Epub ahead of print]Related Articles, LinkOut

Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas
J, Moin S, Israf DA.

The current study was performed to evaluate the antinociceptive and
antiedematogenic properties of andrographolide isolated from the
leaves of Andrographis paniculata using two animal models.
Antinociceptive activity was evaluated using the acetic acid-induced
writhing and the hot-plate tests, while antiedematogenic activity was
measured using the carrageenan-induced paw edema test. Subcutaneous
(s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did
not affect the motor coordination of the experimental animals but
produced significant (p < .05) antinociceptive activity when assessed
using both tests. However, 2 mg/kg naloxone failed to affect the 25
mg/kg andrographolide activity in both tests, indicating that the
activity was modulated via nonopioid mechanisms. Furthermore,
andrographolide showed significant (p < .05) antiedematogenic
activity. In conclusion, the results obtained suggest that
andrographolide has antinociceptive and antiedematogenic activities;
it may be useful for treating pain and inflammation once human studies
are conducted.

PMID: 19689990 [PubMed - as supplied by publisher]

Intracellular glutathione regulates Andrographolide-induced cytotoxicity on hepatoma Hep3B cells

Redox Rep. 2009;14(4):176-84. Related Articles, LinkOut

Ji L, Shen K, Liu J, Chen Y, Liu T, Wang Z.

Key Laboratory of Standardization of Chinese Medicines of Ministry of
Education, Shanghai Key Laboratory of Complex Prescription, Institute
of Chinese Materia Medica, Shanghai University of Traditional Chinese
Medicine, Shanghai, People's Republic China. jll_syc@yahoo.com.cn

Andrographolide (ANDRO), a diterpenoid lactone isolated from the
traditional herbal plant Andrographis paniculata, was reported to
induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL,
Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human
hepatoma-derived Hep3B cells growth through the activation of c-Jun
N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present
investigation was carried out to observe whether cellular reduced
glutathione (GSH) plays important roles in ANDRO-induced apoptosis.
ANDRO initially increased intracellular GSH levels which then
decreased later, while inhibition of cellular GSH synthesis by
L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced
cytotoxicity and apoptosis in Hep3B cells. On the other hand, the
thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular
GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis.
Furthermore, BSO pretreatment augmented ANDRO-decreased expression of
antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this
decrease. Further results showed that ANDRO increased the activity of
the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and
the production of intracellular reactive oxygen species (ROS). Taken
together, this study demonstrates that the intracellular redox system
plays important roles in regulating the cytotoxicity of ANDRO on
hepatoma Hep3B cells.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 19695125 [PubMed - in process]

Oviposition-deterrent, ovicidal, and repellent activities of indigenous plant extracts against Anopheles subpictus Grassi (Diptera: Culicidae)

Parasitol Res. 2009 Aug 26. [Epub ahead of print]

Elango G, Bagavan A, Kamaraj C, Abduz Zahir A, Abdul Rahuman A.

Unit of Bioactive Natural Products, P.G & Research Department of
Zoology, C. Abdul Hakeem College, Vellore District, Melvisharam, 632
509, Tamil Nadu, India.

Insecticides of botanical origin may serve as suitable alternative
biocontrol techniques in the future. The leaf acetone, ethyl acetate,
and methanol extracts of Aegle marmelos (Linn.) Correa ex Roxb,
Andrographis lineata Wallich ex Nees, and Cocculus hirsutus (L.) Diels
were tested for oviposition-deterrent, ovicidal, and repellent
activities against Anopheles subpictus Grassi (Diptera: Culicidae).
The percentage of effective oviposition repellency of 92.60 , 93.04,
95.20, 88.26, 92.80, 94.01, 95.77, 96.93, and 92.54 at 500 ppm and the
lowest repellency of 47.14, 58.00, 56.52, 64.93, 71.09, 66.42, 50.62,
57.62, and 65.73 at 31.25 ppm in acetone, ethyl acetate, and methanol
extracts of Aegle marmelos, Andrographis lineata, and Cocculus
hirsutus, respectively. The oviposition activity index (OAI) value of
acetone, ethyl acetate, and methanol extracts of Aegle marmelos,
Andrographis lineata, and Cocculus hirsutus at 500 ppm were -0.86,
-0.87, -0.90, -0.78, -0.87, -0.86, -0.91, -0.94, and -0.86
respectively. The OAI values revealed that the solvent plant extracts
have deterrent effect, and they caused a remarkable negative response
resulting in oviposition of very few eggs. Mean percent hatchability
of the ovicidal activity was observed 24 h after treatment. The
percent hatchability was inversely proportional to the concentration
of extract and directly proportional to the eggs. Mortality of 100%
with ethyl acetate extract of Aegle marmelos, methanol extracts Aegle
marmelos, Andrographis lineata, and Cocculus hirsutus were exerted at
1,000 ppm. The maximum repellent activity was observed at 500 ppm in
methanol extracts of Aegle marmelos, Andrographis lineata, and ethyl
acetate extract of Cocculus hirsutus, and the mean complete protection
time ranged from 90 to 120 min with the different extracts tested.
These results suggest that the leaf extracts of Aegle marmelos,
Andrographis lineata, and Cocculus hirsutus have the potential to be
used as an ideal ecofriendly approach for the control of the Anopheles
subpictus. Therefore, this study provides first report on the
oviposition, ovicidal, and repellent activities against malaria
vector, Anopheles subpictus of plant extracts from Southern India.

PMID: 19707789 [PubMed - as supplied by publisher]

Intracellular glutathione regulates Andrographolide-induced cytotoxicity on hepatoma Hep3B cells

Redox Rep. 2009;14(4):176-84.

Ji L, Shen K, Liu J, Chen Y, Liu T, Wang Z.

Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic China. jll_syc@yahoo.com.cn

Andrographolide (ANDRO), a diterpenoid lactone isolated from the traditional herbal plant Andrographis paniculata, was reported to induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL, Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human hepatoma-derived Hep3B cells growth through the activation of c-Jun N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in ANDRO-induced apoptosis. ANDRO initially increased intracellular GSH levels which then decreased later, while inhibition of cellular GSH synthesis by L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced cytotoxicity and apoptosis in Hep3B cells. On the other hand, the thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis. Furthermore, BSO pretreatment augmented ANDRO-decreased expression of antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this decrease. Further results showed that ANDRO increased the activity of the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and the production of intracellular reactive oxygen species (ROS). Taken together, this study demonstrates that the intracellular redox system plays important roles in regulating the cytotoxicity of ANDRO on hepatoma Hep3B cells.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 19695125 [PubMed - in process]

Antinociceptive and Antiedematogenic Activities of Andrographolide Isolated From Andrographis paniculata in Animal Models

Biol Res Nurs. 2009 Aug 18. [Epub ahead of print]

Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas
J, Moin S, Israf DA.

The current study was performed to evaluate the antinociceptive and
antiedematogenic properties of andrographolide isolated from the
leaves of Andrographis paniculata using two animal models.
Antinociceptive activity was evaluated using the acetic acid-induced
writhing and the hot-plate tests, while antiedematogenic activity was
measured using the carrageenan-induced paw edema test. Subcutaneous
(s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did
not affect the motor coordination of the experimental animals but
produced significant (p < .05) antinociceptive activity when assessed
using both tests. However, 2 mg/kg naloxone failed to affect the 25
mg/kg andrographolide activity in both tests, indicating that the
activity was modulated via nonopioid mechanisms. Furthermore,
andrographolide showed significant (p < .05) antiedematogenic
activity. In conclusion, the results obtained suggest that
andrographolide has antinociceptive and antiedematogenic activities;
it may be useful for treating pain and inflammation once human studies
are conducted.

PMID: 19689990 [PubMed - as supplied by publisher]

Potency of Andrographolide as an Antitumor Compound in BHC-Induced Liver Damage

Integr Cancer Ther. 2009 Jun;8(2):177-89.

 
Trivedi NP, Rawal UM, Patel BP.

Department of Zoology, School of Sciences, Gujarat University.

Relevance. The present investigation relates to the influence of andrographolide, an active compound of Andrographis paniculata Nees. It reverses an experimental liver carcinogenic condition of mice to normal and might be a potential therapeutic/preventive agent for human liver cancer. Objective. A. paniculata (Kalmegh) is extensively used in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have protective effect against different hepatotoxins. Materials and methods. Histomorphological, ultrastructural, and biochemical studies were performed for the effect of the andrographolide on control mice, mice treated with hexachlorocyclohexane (BHC) only and BHC + andrographolide. Enzymes for liver function tests were analyzed by spectrophotometric method. RESULTS: The BHC experimental model forms an irreversible liver tumor in male mice. The histological and ultrastructural changes observed in andrographolide supplementation emphasize the recovery of the damaged liver. This recovery was also reflected in the neoplastic nodule formation. The activity of phosphorylase and glucose-6-phosphatase in the liver of the andrographolide-supplemented group suggests improved glycogenolysis in liver. Serum glutamate pyruvate transaminase, serum glutamate oxalate transaminase, alkaline phosphatase, acid phosphatase, and gamma-glutamyl transpeptidase showed a significant decrease in andrographolide-supplemented animals as compared with BHC-treated animals, suggesting regenerative effects elicited by andrographolide. CONCLUSION: The study indicates that the regenerative capability elicited by andrographolide is possibly due to its ability to reactivate liver function enzymes that catalyze the reaction of several biochemical and synthetic processes and that it may be useful for severe liver damage conditions.

PMID: 19679627 [PubMed - in process]

Reproductive and Fertility Effects of an Extract of Andrographis paniculata in Male Wistar Rats

Int J Toxicol. 2009 Jul-Aug;28(4):308-17.Related Articles

Allan JJ, Pore MP, Deepak M, Murali B, Mayachari AS, Agarwal A.

MVSc, Department of Pharmacology and Toxicology, R&D Centre, Natural
Remedies Pvt Ltd, 5B, Veerasandra Industrial Area, 19th KM Stone,
Hosur Road, Near Electronic City, Bangalore 560 100, India;
joshua@naturalremedy.com.

The possible effect of extract of Andrographis paniculata Nees (A
paniculata) standardized to >/=10% andrographolide, the main bioactive
component, on male fertility in albino Wistar rats was evaluated, by
orally administering 0, 20, 200, and 1000 mg/kg of body weight per
day, for 65 days prior to mating and 21 days during mating. The
treated groups showed no signs of dose-dependent toxicity. The body
weight gain and feed consumption were not affected at any of the dose
levels. The testosterone levels and fertility indices in treatment
groups were found to be comparable with that of the control indicating
no effect on fertility. Total sperm count and sperm motility were not
affected. The testes and epididymides did not show any gross and
histopathological changes. Based on these findings, it can be
concluded that the no-observed adverse effect level of extract of A
paniculata (>/=10% andrographolide) was found to be more than 1000
mg/kg per day.

PMID: 19636073 [PubMed - in process]

Screening of microfilaricidal effects of plant extracts against Dirofilaria immitis

Res Vet Sci. 2009 Jun 3. [Epub ahead of print]

Merawin LT, Arifah AK, Sani RA, Somchit MN, Zuraini A, Ganabadi S, Zakaria ZA.

Faculty of Veterinary Medicine, 43400 Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Canine dirofilariasis is a common tropical parasitic disease of companion animals, caused by infestation of Dirofilaria immitis filarids within the pulmonary arteries and extending into the right heart. Increased reports of adverse reactions elicited by current microfilaricidal agents against D. immitis such as neurological disorders, circulatory collapse and potential resistance against these agents, warrant the search for new agents in forms of plant extracts. The use of plant extracts in therapeutic medicine is commonly met with scepticism by the veterinary community, thus the lack of focus on its medical potential. This study evaluated the presence of microfilaricidal activities of the aqueous extracts of Zingiber officinale, Andrographis paniculata and Tinospora crispa Miers on D. immitisin vitro at different concentrations; 10mg/ml, 1mg/ml, 100mug/ml, 10mug/ml and 1mug/ml within 24h, by evaluation of relative microfilarial motility as a measure of microfilaricidal activity. All extracts showed microfilaricidal activity with Z. officinale exhibiting the strongest activity overall, followed by A. paniculata and T. crispa Miers. It is speculated that the microfilaricidal mechanism exhibited by these extracts is via spastic paralysis based upon direct observation of the microfilarial motility.

PMID: 19500810 [PubMed - as supplied by publisher]

Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats

Food Chem Toxicol. 2009 Jun 17. [Epub ahead of print]

Akowuah GA, Zhari I, Mariam A, Yam MF.

School of Pharmacy, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.

A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11, 12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g / kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42 +/- 0.09 mug/ml and 1.31 +/- 0.04 mug/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g / kg body weight) followed by CCl(4) administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl(4) did not showed significant alteration (p > 0.05) in plasma total antioxidant status (TAS) as compare to values of control group.

PMID: 19540299 [PubMed - as supplied by publisher]

Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats

Food Chem Toxicol. 2009 Jun 17. [Epub ahead of print]

Akowuah GA, Zhari I, Mariam A, Yam MF.

School of Pharmacy, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.

A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11, 12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g / kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42 +/- 0.09 mug/ml and 1.31 +/- 0.04 mug/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g / kg body weight) followed by CCl(4) administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl(4) did not showed significant alteration (p > 0.05) in plasma total antioxidant status (TAS) as compare to values of control group.

PMID: 19540299 [PubMed - as supplied by publisher]

Screening of microfilaricidal effects of plant extracts against Dirofilaria immitis

1: Res Vet Sci. 2009 Jun 3. [Epub ahead of print]

 
Screening of microfilaricidal effects of plant extracts against Dirofilaria immitis

Merawin LT, Arifah AK, Sani RA, Somchit MN, Zuraini A, Ganabadi S, Zakaria ZA.

Faculty of Veterinary Medicine, 43400 Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Canine dirofilariasis is a common tropical parasitic disease of companion animals, caused by infestation of Dirofilaria immitis filarids within the pulmonary arteries and extending into the right heart. Increased reports of adverse reactions elicited by current microfilaricidal agents against D. immitis such as neurological disorders, circulatory collapse and potential resistance against these agents, warrant the search for new agents in forms of plant extracts. The use of plant extracts in therapeutic medicine is commonly met with scepticism by the veterinary community, thus the lack of focus on its medical potential. This study evaluated the presence of microfilaricidal activities of the aqueous extracts of Zingiber officinale, Andrographis paniculata and Tinospora crispa Miers on D. immitisin vitro at different concentrations; 10mg/ml, 1mg/ml, 100mug/ml, 10mug/ml and 1mug/ml within 24h, by evaluation of relative microfilarial motility as a measure of microfilaricidal activity. All extracts showed microfilaricidal activity with Z. officinale exhibiting the strongest activity overall, followed by A. paniculata and T. crispa Miers. It is speculated that the microfilaricidal mechanism exhibited by these extracts is via spastic paralysis based upon direct observation of the microfilarial motility.

PMID: 19500810 [PubMed - as supplied by publisher]

---

Recherche in vitro d'une activité anti-VIH dans les préparations médicinales traditionnelles: Mémorandum d'une réunion de l'OMS

Bull World Health Organ. 1990; 68(1): 25–31.

PMCID: PMC2393009

 

 No abstract in English. Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

 

| Summary | Page Browse | PDF–1.1M |

Place des plantes médicinales dans la thérapeutique

Norman R. Farnsworth, Olayiwola Akerele, Audrey S. Bingel, Djaja D. Soejarto, and Zhengang Guo

Bull World Health Organ. 1986; 64(2): 159–175.

PMCID: PMC2490930

 

 No abstract in English. Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

 

| Summary | Page Browse | PDF–1.6M |

In vitro screening of traditional medicines for anti-HIV activity: memorandum from a WHO meeting

Bull World Health Organ. 1989; 67(6): 613–618.

PMCID: PMC2491302

 

Many plant products are being used by patients with acquired immunodeficiency syndrome (AIDS) in some countries without any scientific proof that they possess anti-HIV (human immunodeficiency virus) activity. Traditional healers are now offering their remedies for scientific evaluation, and a few studies provide information on the inhibitory activity against HIV of plants such as Viola yedoensis, Arctium lappa, Epimedium grandiflorum, Glycyrrhiza uralensis and Castanospermum australe. Natural products can be selected for biological screening based on ethnomedical use, random collection or a chemotaxonomic approach (i.e., screening of species of the same botanical family for similar compounds), but the follow-up and selection of plants based on literature leads would seem to be the most cost-effective way of identifying plants with anti-HIV activity. No single in vitro screening methodology for anti-HIV activity is ideal and confirmatory assays in multiple systems are needed to examine completely the potential use of a compound. To promote further research in traditional medicine and AIDS, appropriate institutions will be identified where the different activities for the scientific evaluation of plants and their extracts for possible treatment of AIDS can be carried out.

 

| Summary | Page Browse | PDF–1.0M |

Medicinal plants in therapy

Norman R. Farnsworth, Olayiwola Akerele, Audrey S. Bingel, Djaja D. Soejarto, and Zhengang Guo

Bull World Health Organ. 1985; 63(6): 965–981.

PMCID: PMC2536466

One of the prerequisites for the success of primary health care is the availability and use of suitable drugs. Plants have always been a common source of medicaments, either in the form of traditional preparations or as pure active principles. It is thus reasonable for decision-makers to identify locally available plants or plant extracts that could usefully be added to the national list of drugs, or that could even replace some pharmaceutical preparations that need to be purchased and imported. This update article presents a list of plant-derived drugs, with the names of the plant sources, and their actions or uses in therapy.

| Summary | Page Browse | PDF–1.5M | 

Andrographis paniculata and Toxicity

Bibliography on Andrographis paniculata and Toxicity

1: Evaluation of the genotoxic potential and acute oral toxicity of standardized extract of Andrographis paniculata (KalmCold(TM)).

Chandrasekaran CV, Thiyagarajan P, Sundarajan K, Goudar KS, Deepak M, Murali B, Allan JJ, Agarwal A.

Food Chem Toxicol. 2009 May 14. [Epub ahead of print]

PMID: 19447157 [PubMed - as supplied by publisher]

Related Articles

2: Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E.

Das S, Gautam N, Dey SK, Maiti T, Roy S.

Appl Physiol Nutr Metab. 2009 Apr;34(2):124-35.

PMID: 19370042 [PubMed - in process]

Related Articles

3: Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin.

Mishra K, Dash AP, Swain BK, Dey N.

Malar J. 2009 Feb 12;8:26.

PMID: 19216765 [PubMed - indexed for MEDLINE]

Related Articles Free article in PMC | at journal site

4: In vitro nicotine induced superoxide mediated DNA fragmentation in lymphocytes: protective role of Andrographis paniculata Nees.

Das S, Neogy S, Gautam N, Roy S.

Toxicol In Vitro. 2009 Feb;23(1):90-8. Epub 2008 Nov 5.

PMID: 19027060 [PubMed - indexed for MEDLINE]

Related Articles

5: Inhibition of cell-cycle progression in human colorectal carcinoma Lovo cells by andrographolide.

Shi MD, Lin HH, Lee YC, Chao JK, Lin RA, Chen JH.

Chem Biol Interact. 2008 Aug 11;174(3):201-10. Epub 2008 Jun 20.

PMID: 18619950 [PubMed - indexed for MEDLINE]

Related Articles

6: Ethnobotanical survey of folk plants for the treatment of snakebites in Southern part of Tamilnadu, India.

Samy RP, Thwin MM, Gopalakrishnakone P, Ignacimuthu S.

J Ethnopharmacol. 2008 Jan 17;115(2):302-12. Epub 2007 Oct 10.

PMID: 18055146 [PubMed - indexed for MEDLINE]

Related Articles

7: In vitro cytogenetic effects of Andrographis paniculata (kalmegh) on arsenic.

Avani G, Rao MV.

Phytomedicine. 2008 Mar;15(3):221-5. Epub 2007 May 4.

PMID: 17482447 [PubMed - indexed for MEDLINE]

Related Articles

8: Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice.

Sheeja K, Kuttan G.

Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):609-14.

PMID: 17250437 [PubMed - indexed for MEDLINE]

Related Articles

9: Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice.

Singha PK, Roy S, Dey S.

J Ethnopharmacol. 2007 Apr 20;111(1):13-21. Epub 2006 Oct 28.

PMID: 17127022 [PubMed - indexed for MEDLINE]

Related Articles

10: Protective effect of Andrographis paniculata and andrographolide on cyclophosphamide-induced urothelial toxicity.

Sheeja K, Kuttan G.

Integr Cancer Ther. 2006 Sep;5(3):244-51.

PMID: 16880430 [PubMed - indexed for MEDLINE]

Related Articles

11: Semisynthesis and cytotoxic activities of andrographolide analogues.

Jada SR, Hamzah AS, Lajis NH, Saad MS, Stevens MF, Stanslas J.

J Enzyme Inhib Med Chem. 2006 Apr;21(2):145-55. Erratum in: J Enzyme Inhib Med Chem. 2006 Jun;21(3):327.

PMID: 16789428 [PubMed - indexed for MEDLINE]

Related Articles

12: Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers.

See D, Mason S, Roshan R.

Immunol Invest. 2002 May;31(2):137-53.

PMID: 12148949 [PubMed - indexed for MEDLINE]

Related Articles

13: In vitro antifilarial effects of three plant species against adult worms of subperiodic Brugia malayi.

Zaridah MZ, Idid SZ, Omar AW, Khozirah S.

J Ethnopharmacol. 2001 Nov;78(1):79-84.

PMID: 11585692 [PubMed - indexed for MEDLINE]

Related Articles

14: Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice.

Trivedi NP, Rawal UM.

Indian J Exp Biol. 2001 Jan;39(1):41-6.

PMID: 11349524 [PubMed - indexed for MEDLINE]

Related Articles

15: Targeting of liposomal andrographolide to L. donovani-infected macrophages in vivo.

Sinha J, Mukhopadhyay S, Das N, Basu MK.

Drug Deliv. 2000 Oct-Dec;7(4):209-13.

PMID: 11195427 [PubMed - indexed for MEDLINE]

Related Articles

16: Aspects of the male reproductive toxicity/male antifertility property of andrographolide in albino rats: effect on the testis and the cauda epididymidal spermatozoa.

Akbarsha MA, Murugaian P.

Phytother Res. 2000 Sep;14(6):432-5.

PMID: 10960897 [PubMed - indexed for MEDLINE]

Related Articles

17: Testicular toxicity assessment of Andrographis paniculata dried extract in rats.

Burgos RA, Caballero EE, Sánchez NS, Schroeder RA, Wikman GK, Hancke JL.

J Ethnopharmacol. 1997 Nov;58(3):219-24.

PMID: 9421258 [PubMed - indexed for MEDLINE]

Related Articles

18: Andrographolide protects rat hepatocytes against paracetamol-induced damage.

Visen PK, Shukla B, Patnaik GK, Dhawan BN.

J Ethnopharmacol. 1993 Oct;40(2):131-6.

PMID: 8133653 [PubMed - indexed for MEDLINE]

Related Articles

19: Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata.

Kapil A, Koul IB, Banerjee SK, Gupta BD.

Biochem Pharmacol. 1993 Jul 6;46(1):182-5.

PMID: 8347130 [PubMed - indexed for MEDLINE]

Related Articles

20: Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats.

Handa SS, Sharma A.

Indian J Med Res. 1990 Aug;92:284-92.

PMID: 2228075 [PubMed - indexed for MEDLINE]

Related Articles

21: [Pharmacological studies on thirteen kinds of injections from Andrographis paniculata. I. Antipyretic, anti-inflammatory effects and toxicity]

Deng WL.

Zhong Yao Tong Bao. 1985 Jul;10(7):38-42. Chinese. No abstract available.

PMID: 2932241 [PubMed - indexed for MEDLINE]

Related Articles

22: Andrographolide and kalmegh (Andrographis paniculata) extract: in vivo and in vitro effect on hepatic lipid peroxidation.

Choudhury BR, Poddar MK.

Methods Find Exp Clin Pharmacol. 1984 Sep;6(9):481-5.

PMID: 6513681 [PubMed - indexed for MEDLINE]

Related Articles

23: Filaricidal properties of a wild herb, Andrographis paniculata.

Dutta A, Sukul NC.

J Helminthol. 1982 Jun;56(2):81-4.

PMID: 7201486 [PubMed - indexed for MEDLINE]

Related Articles

Evaluation of the genotoxic potential and acute oral toxicity of standardized extract of Andrographis paniculata

Food Chem Toxicol. 2009 May 14.

Evaluation of the genotoxic potential and acute oral toxicity of standardized extract of Andrographis paniculata (KalmCold(TM)).

Chandrasekaran CV, Thiyagarajan P, Sundarajan K, Goudar KS, Deepak M, Murali B, Allan JJ, Agarwal A.

R & D centre, Natural Remedies Pvt. Ltd., Bangalore, India.

Andrographis paniculata was used in the traditional medicine for cold and influenza remedy. The main endeavor in this study was to assess the genotoxicity of the standardized extract of A. paniculata (KalmCold(TM)) through three different in vitro tests: Ames; Chromosome aberration (CA), and Micronucleus (MN). Ames test was performed at 5000 mug/ml, 1581 mug/ml, 500 mug/ml, 158 mug/ml, 50 mug/ml and 16 mug/ml, while the clastogenicity tests were performed at 80 mug/ml, 26.6 mug/ml and 8.8 mug/ml for short-term treatment without S9; 345 mug/ml, 115 mug/ml and 38.3 mug/ml for short-term treatment with S9; and 46 mug/ml, 15.3 mug/ml and 5.1 mug/ml for long-term without S9 using DMSO as a vehicle control. Results of Ames test showed that KalmCold(TM) did not induce mutations both in the presence and absence of S9 in Salmonella typhimurium mutant strains TA98 and TAMix. In CA and MN, KalmCold(TM) did not induce clastogenicity in CHO-K1 cells in vitro. Based on our results, it is evident that KalmCold(TM) is genotoxically safe. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg of KalmCold(TM) and observed for signs of toxicity for 14 days. KalmCold(TM) did not produce any treatment- related toxic effects in rats.

PMID: 19447157 [PubMed - as supplied by publisher]

Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression

Chem Biol Interact. 2009 May 5. [Epub ahead of print]

Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression.

Shi MD, Lin HH, Chiang TA, Tsai LY, Tsai SM, Lee YC, Chen JH.

Pathology and Laboratory Medicine, Yongkang Veterans Hospital, Tainan, Taiwan; Department of Medical Laboratory and Biotechnology Science, College of Health Sciences Kaohsiung Medical University, Kaohsiung, Taiwan.

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to have potent anti-cancer activity against human colorectal carcinoma Lovo cells by inhibiting cell-cycle progression. To further investigate the mechanism basis for the anti-cancer properties of Andro, it was used to examine the effect on migration and invasion in Lovo cells. The results of wound-healing assay and in vitro transwell assay revealed that Andro inhibited dose-dependently the migration and invasion of lovo cells under non-cytotoxic concentrations. Using zymographic assay and RT-PCR, the results revealed that Andro diminished the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The down-regulation of MMP-7 appeared to be via the inactivation of activator protein-1 (AP-1) since the treatment with Andro suppressed the nuclear protein level of AP-1, which was accompanied by a decrease in DNA binding level of the factor. Taken together, these results indicated that Andro reduces the MMP-7-mediated cellular events in Lovo cells, and provided a new mechanism for its anti-cancer activity.

PMID: 19426720 [PubMed - as supplied by publisher]

Identification of four urea adducts of andrographolide in humans

Drug Metab Lett. 2008 Dec;2(4):261-8.

Identification of four urea adducts of andrographolide in humans.

Cui L, Chan W, Qiu F, Cai Z, Yao X.

Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, China.

Andrographolide is a component of a famous traditional Chinese herbal medicine Andrographis paniculate (Burm) Nees. In this study, the metabolites of andrographolide in human urine after oral administration were investigated. Four urea adducts were isolated by chromatography methods and identified by high-resolution mass spectra, 1 D and 2D NMR spectroscopy.

Publication Types:

• Clinical Trial

PMID: 19356103 [PubMed - indexed for MEDLINE]

Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata

Appl Physiol Nutr Metab. 2009 Apr;34(2):124-35.

Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E.

Das S, Gautam N, Dey SK, Maiti T, Roy S.

Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal, India.

Mitochondria are the crossroads of several crucial cellular activities; they produce considerable quantities of superoxide radical and hydrogen peroxide, which can damage important macromolecules. Nicotine affects a variety of cellular processes, from induction of gene expression to modulation of enzymatic activities. The aim of this study was to elucidate the protective effects of andrographolide (ANDRO) aqueous extract (AE-Ap) of Andrographis paniculata, and vitamin E on nicotine-induced brain mitochondria. In this investigation, nicotine (1 mg.kg body mass-1.day-1) was treated, for the period of 7 days, simultaneously with 2 A. paniculata products, ANDRO and AE-Ap (250 mg.kg body mass-1.day-1); and vitamin E (50 mg.kg body mass-1.day-1) was supplemented in different group of male Wistar rats. The activities of mitochondrial electron transport chain (Mito-ETC) complexes (I, II, III), nitric oxide production, superoxide anion, catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, and concentrations of reduced glutathione and oxidized glutathione were measured in discrete regions of brain (the cerebral hemisphere, cerebellum, diencephalons, and brain stem). The study revealed that nicotine inhibits the Mito-ETC complexes and produces nitric oxide, which suppressed the mitochondrial oxidative stress scavenger system in different brain regions. In these circumstances, lipid peroxidation and protein oxidation were noted in different discrete regions of brain mitochondria. ANDRO, AE-Ap, and vitamin E showed the protective potentiality against nicotine toxicity. The analysis of such alterations is important in determining the basis of normal dysfunction in the brain associated with nicotine toxicity, which could be ameliorated by A. paniculata and vitamin E, and may help to develop therapeutic means against nicotine-induced disorders.

PMID: 19370042 [PubMed - in process]

Prophylactic effect of Andrographis paniculata extracts against Streptococcus agalactiae infection

J Biosci Bioeng. 2009 May;107(5):579-82.

Prophylactic effect of Andrographis paniculata extracts against Streptococcus agalactiae infection in Nile tilapia (Oreochromis niloticus).

Rattanachaikunsopon P, Phumkhachorn P.

Department of Biological Science, Faculty of Science, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani 34190, Thailand. rattanachaikunsopon@yahoo.com

Six herbs were assessed for their antimicrobial activity against Streptococcus agalactiae, a major fish pathogen causing streptococcosis. Each herb was extracted with 3 solvents: water, 95% ethanol, and methanol. Using swab paper disc assays, aqueous extracts of Andrographis paniculata and Allium sativum produced the largest (27.5 mm) and smallest (10.3 mm) inhibition zones, respectively. Determination of minimal inhibitory concentration (MIC) of herb extracts against S. agalactiae showed that the aqueous extract of A. paniculata had the lowest MIC value (31.25 microg/mL). Aqueous extract of A. sativum was the only herb extract with a MIC > 500 microg/mL. Based on mortalities in 2 weeks after intraperitoneal S. agalactiae injection, the median lethal dose (LD(50)) of S. agalactiae for Nile tilapia (Oreochromis niloticus) was 3.79 x 10(5) CFU/mL. In vivo experiments showed that fish feed supplemented with either A. paniculata leaf powder or dried matter of A. paniculata aqueous extract reduced mortality of S. agalactiae infected Nile tilapia. In addition, no mortality was found in fish receiving dried matter of A. paniculata aqueous extract supplemented feeds at ratios (w/w) of 4:36 and 5:35. During 2 weeks of feeding with A. paniculata supplemented feeds, no adverse effects on appearance, behavior, or feeding responses were observed.

PMID: 19393561 [PubMed - in process]

Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms

Clin Rheumatol. 2009 Apr 29. [Epub ahead of print]

Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial.

Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Cáceres DD.

Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, P.O. Box 567, Valdivia, Chile, rburgos1@uach.cl.

Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin(R)) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint -0.13 95% confidence interval (CI; -0.22 to 0.06; p = 0.001), number of swollen joints -0.15 95%CI (-0.29 to -0.02; p = 0.02), total grade of swollen joint -0.27 95%CI (-0.48 to -0.07; p = 0.010), number of tender joints -0.25 95%CI (-0.48 to -0.02; p = 0.033), total grade of swollen joints -0.27 95%CI (-0.48 to -0.07; p = 0.01), total grade of tender joints -0.47 95%CI (-0.77 to -0.17; p = 0.002) and HAQ -0.52 95%CI (-0.82 to -0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health questionnaires was observed within the group with the active drug. Moreover, it was associated to a reduction of rheumatoid factor, IgA, and C4. These findings suggest that A. paniculata could be a useful "natural complement" in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.

PMID: 19408036 [PubMed - as supplied by publisher]