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]