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Old 05-23-2012, 10:43 AM   #1
Rich66
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Andrographolide

Clin Exp Pharmacol Physiol. 2012 Mar;39(3):300-10. doi: 10.1111/j.1440-1681.2011.05633.x.
Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer.

Lim JC, Chan TK, Ng DS, Sagineedu SR, Stanslas J, Wong WS.
Source

Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.

Abstract

1.  Andrographis paniculata (Burm. f) Nees, commonly known as 'king of bitters', is a herbaceous plant belonging to the Family Acanthaceae. It has been widely used for centuries in Asian countries like China, India, Thailand and Malaysia for the treatment of sore throat, flu and upper respiratory tract infections. 2. Andrographolide, 14-deoxy-11,12-didehydroandrographolide and neoandrographolide are examples of the major labdane diterpenoids isolated from A. paniculata. These bioactive molecules have exhibited varying degrees of anti-inflammatory and anticancer activities in both in vitro and in vivo experimental models of inflammation and cancer. 3. Extensive libraries of andrographolide analogues have been synthesised mainly by modifying the α,β-unsaturated γ-butyrolactone moiety, the two double bonds Δ(8,(17)) and Δ(12,(13)) and the three hydroxyls at C-3 (secondary), C-14 (allylic) and C-19 (primary). Many of these synthetic analogues exhibit superior anticancer activity over the naturally occurring andrographolides. 4. Andrographolide and its derivatives have been shown to have anti-inflammatory effects in experimental models of asthma, stroke and arthritis, as well as in patients with upper respiratory tract infections. Andrographolide reduces the production of cytokines, chemokines, adhesion molecules, nitric oxide and lipid mediators, probably via inhibition of the nuclear factor (NF)-κB signalling pathway. 5. The anticancer mechanisms for andrographolide include inhibition of Janus tyrosine kinases-signal transducers and activators of transcription, phosphatidylinositol 3-kinase and NF-κB signalling pathways, suppression of heat shock protein 90, cyclins and cyclin-dependent kinases, metalloproteinases and growth factors, and the induction of tumour suppressor proteins p53 and p21, leading to inhibition of cancer cell proliferation, survival, metastasis and angiogenesis. 6. Andrographolide drug discovery is a promising strategy for the development of a novel class of anti-inflammatory and anticancer drugs.
© 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

PMID:
22017767
[PubMed - in process]
Genes Cancer. 2011 Feb;2(2):151-9.
Andrographolide targets androgen receptor pathway in castration-resistant prostate cancer.

Liu C, Nadiminty N, Tummala R, Chun JY, Lou W, Zhu Y, Sun M, Evans CP, Zhou Q, Gao AC.

Free PMC Article

Source

Department of Urology, University of California at Davis, Sacramento, CA, USA.

Abstract

Androgen receptor (AR) signaling not only plays a pivotal role in the development of androgen-dependent prostate cancer but is also important in the growth and survival of castration-resistant prostate cancer (CRPC). The first line of treatment of androgen-dependent prostate cancer is the use of androgen deprivation therapy. However, most patients will eventually relapse due to development of CRPC. Thus, development of a strategy to target AR for treatment of CRPC is urgently needed. The authors have previously identified andrographolide as an inhibitor of interleukin-6, which can suppress tumor growth of prostate cancer cells by screening compounds from the Prestwick Natural compound library. In this study, they identified that andrographolide can inhibit AR expression and prostate cancer cell growth and induce apoptosis. Andrographolide is able to down-regulate AR expression at both mRNA and protein levels, prevents its nuclear translocation, and inhibits transactivation of its target genes. Andrographolide prevents the binding of Hsp90 to AR, resulting in proteasome-mediated AR degradation. Furthermore, andrographolide inhibits castration-resistant C4-2 cell growth by reducing AR expression and activity. Thus, andrographolide can be developed as a potential therapeutic agent for prostate cancer by inhibition of androgen receptor signaling.

PMID:
21779488


Planta Med. 2010 Nov;76(16):1827-33. Epub 2010 Jun 10.
Andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity.

Chao HP, Kuo CD, Chiu JH, Fu SL.

LINK

Source

Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.

Abstract

Andrographolide, a major constituent of Andrographis paniculata, was previously shown to exhibit anti-inflammatory, antiviral, and anticancer activities. The anticancer activity of andrographolide includes growth suppression, apoptosis promotion, antiangiogenesis, and antitransformation. However, the effect of andrographolide on cancer metastasis, the most malignant feature of cancer, has not been elucidated extensively. In the present study, we demonstrated that andrographolide at nontoxic to subtoxic concentrations (0.3-3 µM) suppressed the invasion ability of CT26 cells in Matrigel-based invasion assays. In addition, the expression of cell adhesion regulators (β-catenin and ILK) was not altered by andrographolide treatment. However, andrographolide indeed inhibited matrix metalloproteinase 2 (MMP2) activity without affecting its expression. Furthermore, the activation of ERK, but not Akt, was attenuated by andrographolide treatment. Notably, a similar inhibitory effect of andrographolide on the invasion and MMP2 activity of the human colon cancer cell line HT29 was also observed. In summary, our results indicate that andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity.
© Georg Thieme Verlag KG Stuttgart · New York.





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.

Free PMC Article

Source

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

Abstract

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]

PMCID:
PMC3139959


Quote:
The compound is able to induce a G0/G1 cellcycle arrest in various kinds of cancer cells, activate the death receptor pathways, induce TRAIL mediated apoptosis, activate p53 via enhanced phosphorylation and cause
inhibition of NF-κB transcriptional factors and various angiogenic factors. It also exerts strong immunomodulatory effects against cancer cells in addition to its cytotoxic effects;
a property which is similar to other anticancer agents including doxorubicin, mitomycin, cisplatin, and so forth.
Apart from acting on various pathways to obliterate cancer cells; it also exerts a protective effect on normal cells saving
them from induced toxicity, in comparison to the contrary effect against cancer cells.






Chin Med. 2010 May 13;5:17.
Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian).

Chao WW, Lin BF.
Source

Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan. bifong@ntu.edu.tw.


Free PMC Article

Abstract

Andrographis paniculata (Burm. f.) Nees (Acanthaceae) is a medicinal plant used in many countries. Its major constituents are diterpenoids, flavonoids and polyphenols. Among the single compounds extracted from A. paniculata, andrographolide is the major one in terms of bioactive properties and abundance. Among the andrographolide analogues, 14-deoxy-11,12-didehydroandrographolide is immunostimulatory, anti-infective and anti-atherosclerotic; neoandrographolide is anti-inflammatory, anti-infective and anti-hepatotoxic; 14-deoxyandrographolide is immunomodulatory and anti-atherosclerotic. Among the less abundant compounds from A. paniculata, andrograpanin is both anti-inflammatory and anti-infective; 14-deoxy-14,15-dehydroandrographolide is anti-inflammatory; isoandrographolide, 3,19-isopropylideneandrographolide and 14-acetylandrographolide are tumor suppressive; arabinogalactan proteins are anti-hepatotoxic. The four flavonoids from A. paniculata, namely 7-O-methylwogonin, apigenin, onysilin and 3,4-dicaffeoylquinic acid are anti-atherosclerotic.

PMID:
20465823
[PubMed]

PMCID:
PMC2881933




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Old 05-23-2012, 10:44 AM   #2
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