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

Malar J. 2009 Feb 12;8(1):26. [Epub ahead of print]

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

ABSTRACT: BACKGROUND: Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. METHODS: Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. RESULTS: The 50% inhibitory concentration (IC50) of AP (7.2 mug/ml) was found better than HC (10.8 mug/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. CONCLUSION: Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

PMID: 19216765 [PubMed - as supplied by publisher]

A Novel Anti-inflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-{kappa}B Pathway

Am J Respir Crit Care Med. 2009 Feb 6. [Epub ahead of print]

Bao Z, Guan S, Cheng C, Wu S, Wong SH, Kemeny DM, Leung BP, Wong WS.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore; Division of Respiratory Medicine, The First Affiliated-Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

RATIONALE: Persistent activation of nuclear factor (NF)-kappaB has been associated with the development of asthma. Andrographolide, the principal active component of a medicinal plant Andrographis paniculata, has been shown to inhibit NF-kappaB activity. OBJECTIVES: We hypothesized that andrographolide may attenuate allergic asthma via inhibition of the NF-kappaB signaling pathway. METHODS: BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Serum IgE levels were also determined. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. MEASUREMENTS AND MAIN RESULTS: Andrographolide dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid, and reduced serum level of ovalbumin-specific IgE. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, chitinases, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, andrographolide blocked TNF-alpha-induced phosphorylation of inhibitory kappaB (IkappaB) kinase-beta (IKKbeta), and downstream IkappaBalpha degradation, p65 subunit of NF-kappaB phosphorylation, and p65 nuclear translocation and DNA-binding activity. Similarly, andrographolide blocked p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. CONCLUSIONS: Our findings implicate a potential therapeutic value of andrographolide in the treatment of asthma and it may act by inhibiting NF-kappaB pathway at the level of IKKbeta activation.

PMID: 19201922 [PubMed - as supplied by publisher]

Evaluation of beneficial effects of antioxidant properties of aqueous leaf extract of Andrographis paniculata in STZ-induced diabetes

Pak J Pharm Sci. 2009 Jan;22(1):49-52.

Dandu AM, Inamdar NM.

Department of Pharmacology, Al-Ameen college of Pharmacy, Bangalore-560027, Karnataka, India.

The beneficial effects of antioxidant properties Andrographis paniculata (Andrographis) were studied in the diabetic animals. Hyperglycemia, characteristic feature of diabetes mellitus leads to decreased antioxidant defense and hence development of oxidative stress, which in involved in the etiology of development of diabetic complications. The evidences suggest that good glycemic control and/or use of antioxidants may play an important role in the prevention of complications associated with diabetes. Diabetes was induced with single intraperitoneal injection of streptozotocin (45 mg/kg, i.p) dissolved in freshly prepared citrate buffer (pH 4.5), resulted in elevation of blood glucose levels, decrease in the superoxide dismutase and catalase activity. Oral administration of Andrographis (400 mg/kg, p.o) resulted in significant decrease in the blood glucose levels and increase in the activity of SOD and catalase. In conclusion Andrographis decreased the blood glucose levels in diabetic animals may be due to its antioxidant properties.

PMID: 19168420 [PubMed - in process]

Laboratory study on larvicidal activity of indigenous plant extracts against Anopheles subpictus and Culex tritaeniorhynchus

Parasitol Res. 2009 Jan 23. [Epub ahead of print]

Elango G, Rahuman AA, Bagavan A, Kamaraj C, Zahir AA, Venkatesan C.

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

Anopheles subpictus and Culex tritaeniorhynchus have developed resistance to various synthetic insecticides, making its control increasingly difficult. Insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. The leaf acetone, chloroform, ethyl acetate, hexane, and methanol extracts of Aegle marmelos (Linn.) Correa ex Roxb, Andrographis lineata Wallich ex Nees., Andrographis paniculata (Burm.f.) Wall. ex Nees., Cocculus hirsutus (L.) Diels, Eclipta prostrata L., and Tagetes erecta L. were tested against fourth-instar larvae of malaria vector, A. subpictus Grassi and Japanese encephalitis vector, C. tritaeniorhynchus Giles (Diptera: Culicidae). All plant extracts showed moderate larvicidal effects after 24 h of exposure at 1,000 ppm; however, the highest larval mortality was found in leaf ethyl acetate of A. marmelos, E. prostrata, hexane, methanol of A. paniculata and C. hirsutus against the larvae of A. subpictus (LC(50) = 167.00, 78.28, 67.24, 142.83 ppm; LC(90) = 588.31, 360.75, 371.91, and 830.01 ppm) and against the larvae of C. tritaeniorhynchus (LC(50) = 99.03, 119.89, 88.50, 105.19 ppm; LC(90) = 479.23, 564.85, 416.39, and 507.86 ppm), respectively. These results suggest that the leaf hexane extract of A. paniculata and ethyl acetate extract of E. prostrata have the potential to be used as an ideal eco-friendly approach for the control of the A. subpictus and C. tritaeniorhynchus. Therefore, this study provides first report on the mosquito larvicidal activity of plant extracts against vectors from Southern India.

PMID: 19165502 [PubMed - as supplied by publisher]

Synthesis and evaluation of antibacterial activities of andrographolide analogues

Eur J Med Chem. 2008 Dec 25. [Epub ahead of print]

    Jiang X, Yu P, Jiang J, Zhang Z, Wang Z, Yang Z, Tian Z, Wright SC, Larrick JW, Wang Y.

    Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China.

    Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used for many years to treat a variety of diseases including bacterial and viral infections. Andro was recently reported to act by inhibiting the bacterial quorum sensing system. We have synthesized several Andro analogues and investigated their antibacterial activity and mechanism of action. The new compounds were found to be much more potent than the parent Andro in inhibiting bacterial growth and quorum sensing system. Compounds 5 and 7 significantly reduced virulence factor production. Compound 7 completely inhibited Pseudomonas aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic activity with conventional antibiotics. These findings suggest that compound 7 may be the basis for future drug development to combat the unmet needs of virulence factor production, biofilm formation and antibiotic resistance.

PMID: 19152987 [PubMed - as supplied by publisher]

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

Malar J. 2009 Feb 12;8(1):26. [Epub ahead of print]

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

ABSTRACT: BACKGROUND: Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. METHODS: Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. RESULTS: The 50% inhibitory concentration (IC50) of AP (7.2 mug/ml) was found better than HC (10.8 mug/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. CONCLUSION: Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

PMID: 19216765 [PubMed - as supplied by publisher]

Antioxidant, antioedema and analgesic activities of Andrographis paniculata extracts and their active constituent andrographolide

Phytother Res. 2009 Jan 13. [Epub ahead of print]

Lin FL, Wu SJ, Lee SC, Ng LT.

Department of Pharmacy, Tajen University, Pingtung, Taiwan.

Andrographis paniculata (AP), a popular ingredient of Oriental folk medicine, is commonly used for treating infection, inflammation, fever and diarrhoea. In this study, extracts prepared from cultivated AP and their active constituent andrographolide were evaluated for antioxidant, antioedema and analgesic activities. The results showed that the aqueous AP extract (AP-H(2)O) exhibited a greater antioxidant activity than the ethanol AP extract (AP-EtOH) in all model systems tested. At a concentration of 50 microg/mL, the free radical scavenging, xanthine oxidase inhibition and antilipid peroxidation activities for AP-H(2)O were 66.8%, 57.3% and 65.3%, respectively, and for AP-EtOH were 57.8%, 52.6% and 34.2%, respectively. At a dosage of 100 mg/kg, AP-H(2)O and andrographolide, but not AP-EtOH, showed antioedema and analgesic activities. In phytochemical analysis, AP-H(2)O showed a higher concentration of total flavanoid but a lower phenol content than AP-EtOH. In conclusion, AP-H(2)O was more potent than AP-EtOH in antioxidant activities. Furthermore, compared with andrographolide, AP-H(2)O as an extract also appears to possess potent antioedema and analgesic activities. Copyright (c) 2009 John Wiley & Sons, Ltd.

PMID: 19142986 [PubMed - as supplied by publisher]

Synthesis and evaluation of antibacterial activities of andrographolide analogues

Eur J Med Chem. 2008 Dec 25. [Epub ahead of print]

Jiang X, Yu P, Jiang J, Zhang Z, Wang Z, Yang Z, Tian Z, Wright SC, Larrick JW, Wang Y.

Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China.

Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used for many years to treat a variety of diseases including bacterial and viral infections. Andro was recently reported to act by inhibiting the bacterial quorum sensing system. We have synthesized several Andro analogues and investigated their antibacterial activity and mechanism of action. The new compounds were found to be much more potent than the parent Andro in inhibiting bacterial growth and quorum sensing system. Compounds 5 and 7 significantly reduced virulence factor production. Compound 7 completely inhibited Pseudomonas aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic activity with conventional antibiotics. These findings suggest that compound 7 may be the basis for future drug development to combat the unmet needs of virulence factor production, biofilm formation and antibiotic resistance.

PMID: 19152987 [PubMed - as supplied by publisher]

Laboratory study on larvicidal activity of indigenous plant extracts against Anopheles subpictus and Culex tritaeniorhynchus.

Parasitol Res. 2009 Jan 23. [Epub ahead of print]

Elango G, Rahuman AA, Bagavan A, Kamaraj C, Zahir AA, Venkatesan C.
Unit of Bioactive Natural Products, P.G. and Research Department of Zoology, C.Abdul Hakeem College, Melvisharam 632 509, Vellore District, Tamil Nadu, India.

Anopheles subpictus and Culex tritaeniorhynchus have developed resistance to various synthetic insecticides, making its control increasingly difficult. Insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. The leaf acetone, chloroform, ethyl acetate, hexane, and methanol extracts of Aegle marmelos (Linn.) Correa ex Roxb, Andrographis lineata Wallich ex Nees., Andrographis paniculata (Burm.f.) Wall. ex Nees., Cocculus hirsutus (L.) Diels, Eclipta prostrata L., and Tagetes erecta L. were tested against fourth-instar larvae of malaria vector, A. subpictus Grassi and Japanese encephalitis vector, C. tritaeniorhynchus Giles (Diptera: Culicidae). All plant extracts showed moderate larvicidal effects after 24 h of exposure at 1,000 ppm; however, the highest larval mortality was found in leaf ethyl acetate of A. marmelos, E. prostrata, hexane, methanol of A. paniculata and C. hirsutus against the larvae of A. subpictus (LC(50) = 167.00, 78.28, 67.24, 142.83 ppm; LC(90) = 588.31, 360.75, 371.91, and 830.01 ppm) and against the larvae of C. tritaeniorhynchus (LC(50) = 99.03, 119.89, 88.50, 105.19 ppm; LC(90) = 479.23, 564.85, 416.39, and 507.86 ppm), respectively. These results suggest that the leaf hexane extract of A. paniculata and ethyl acetate extract of E. prostrata have the potential to be used as an ideal eco-friendly approach for the control of the A. subpictus and C. tritaeniorhynchus. Therefore, this study provides first report on the mosquito larvicidal activity of plant extracts against vectors from Southern India.

    PMID: 19165502 [PubMed - as supplied by publisher]

Evaluation of beneficial effects of antioxidant properties of aqueous leaf extract of Andrographis paniculata in STZ-induced diabetes

Pak J Pharm Sci. 2009 Jan;22(1):49-52.

    Dandu AM, Inamdar NM.

    Department of Pharmacology, Al-Ameen college of Pharmacy, Bangalore-560027, Karnataka, India.

    The beneficial effects of antioxidant properties Andrographis paniculata (Andrographis) were studied in the diabetic animals. Hyperglycemia, characteristic feature of diabetes mellitus leads to decreased antioxidant defense and hence development of oxidative stress, which in involved in the etiology of development of diabetic complications. The evidences suggest that good glycemic control and/or use of antioxidants may play an important role in the prevention of complications associated with diabetes. Diabetes was induced with single intraperitoneal injection of streptozotocin (45 mg/kg, i.p) dissolved in freshly prepared citrate buffer (pH 4.5), resulted in elevation of blood glucose levels, decrease in the superoxide dismutase and catalase activity. Oral administration of Andrographis (400 mg/kg, p.o) resulted in significant decrease in the blood glucose levels and increase in the activity of SOD and catalase. In conclusion Andrographis decreased the blood glucose levels in diabetic animals may be due to its antioxidant properties.

    PMID: 19168420 [PubMed - in process]

A Novel Anti-inflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-{kappa}B Pathway

Am J Respir Crit Care Med. 2009 Feb 6. [Epub ahead of print]

Bao Z, Guan S, Cheng C, Wu S, Wong SH, Kemeny DM, Leung BP, Wong WS.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore; Division of Respiratory Medicine, The First Affiliated-Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

RATIONALE: Persistent activation of nuclear factor (NF)-kappaB has been associated with the development of asthma. Andrographolide, the principal active component of a medicinal plant Andrographis paniculata, has been shown to inhibit NF-kappaB activity. OBJECTIVES: We hypothesized that andrographolide may attenuate allergic asthma via inhibition of the NF-kappaB signaling pathway. METHODS: BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Serum IgE levels were also determined. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. MEASUREMENTS AND MAIN RESULTS: Andrographolide dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid, and reduced serum level of ovalbumin-specific IgE. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, chitinases, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, andrographolide blocked TNF-alpha-induced phosphorylation of inhibitory kappaB (IkappaB) kinase-beta (IKKbeta), and downstream IkappaBalpha degradation, p65 subunit of NF-kappaB phosphorylation, and p65 nuclear translocation and DNA-binding activity. Similarly, andrographolide blocked p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. CONCLUSIONS: Our findings implicate a potential therapeutic value of andrographolide in the treatment of asthma and it may act by inhibiting NF-kappaB pathway at the level of IKKbeta activation.

PMID: 19201922 [PubMed - as supplied by publisher]

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

Malar J. 2009 Feb 12;8(1):26. [Epub ahead of print]

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

ABSTRACT: BACKGROUND: Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. METHODS: Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. RESULTS: The 50% inhibitory concentration (IC50) of AP (7.2 mug/ml) was found better than HC (10.8 mug/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. CONCLUSION: Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

PMID: 19216765 [PubMed - as supplied by publisher]