36
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Shatavarins (containing Shatavarin IV) with anticancer activity from the roots of Asparagus racemosus

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objectives:

          The anticancer activity of shatavarins (containing shatavarin IV) isolated from the roots of Asparagus racemosus (Wild) was evaluated using in vitro and in vivo experimental models.

          Material and Methods:

          The shatavarin IV was isolated from ethyl acetate insoluble fraction (AR-2B) of chloroform:methanol (2:1) (AR-2) extract of A. racemosus roots. The cytotoxicity ( in vitro) of shatavarin IV and other shatavarins rich fraction was carried out using of MTT assay using MCF-7 (human breast cancer), HT-29 (human colon adenocarcinoma), and A-498 (human kidney carcinoma) cell lines. The in vivo anticancer activity of shatavarins (containing shatavarin IV) was evaluated against Ehrlich ascites carcinoma (EAC) tumor bearing mice.

          Results:

          The isolated shatavarin IV (84.69 %) along with shatavarins rich fraction, coded AR-2B containing 5.05% shatavarin IV showed potent cytotoxicity. Oral administration of AR-2B to tumor bearing mice at doses of 250 and 500 mg/kg body weight for 10 days, showed significant reduction in percent increase in body weight, tumor volume, packed cell volume, viable tumor cell count, and increased non-viable cell count when compared to the untreated mice of the EAC control group. The restoration of hematological parameters towards normalcy was also observed.

          Conclusion:

          The result suggests that the shatavarins (containing shatavarin IV) rich fraction (AR-2B) exhibits significant anticancer activity in both in vitro and in vivo experimental models.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Advances in cancer therapy with plant based natural products.

          Natural Products have long been a fertile source of cure for cancer, which is projected to become the major causes of death in this century. However, there is a continuing need for development of new anticancer drugs, drug combinations and chemotherapy strategies, by methodical and scientific exploration of enormous pool of synthetic, biological and natural products. There are at least 250,000 species of plants out of which more than one thousand plants have been found to possess significant anticancer properties. While many molecules obtained from nature have shown wonders, there are a huge number of molecules that still either remains to be trapped or studied in details by the medicinal chemists. The article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of nature derived anti-cancer agents at the molecular, cellular and physiological levels. Taxol, one of the most outstanding agents, has been found beneficial in treatment of refractory ovarian, breast and other cancers. Another prominent molecule includes Podophyllotoxin. Synthetic modification of this molecule led to the development of Etoposide, known to be effective for small cell cancers of the lungs and testes. Camptothecin isolated from Camptotheca acuminata also have been extensively studied. Other important molecules discussed include Vincristine, Vinblastine, Colchicine, Ellipticine and Lepachol along with Flavopiridol, a semi-synthetic analogue of the chromone alkaloid Rohitukine from India, a pyridoindole alkaloid from leaves of Ochrosia species and many more. The review also deals with the lesser-known plants of sub-Himalayan region.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis.

            Guggulsterone, derived from Commiphora mukul and used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, has been recently shown to antagonize the farnesoid X receptor and decrease the expression of bile acid-activated genes. Because activation of NF-kappaB has been closely linked with inflammatory diseases affected by guggulsterone, we postulated that it must modulate NF-kappaB activation. In the present study, we tested this hypothesis by investigating the effect of this steroid on the activation of NF-kappaB induced by inflammatory agents and carcinogens. Guggulsterone suppressed DNA binding of NF-kappaB induced by tumor necrosis factor (TNF), phorbol ester, okadaic acid, cigarette smoke condensate, hydrogen peroxide, and interleukin-1. NF-kappaB activation was not cell type-specific, because both epithelial and leukemia cells were inhibited. Guggulsterone also suppressed constitutive NF-kappaB activation expressed in most tumor cells. Through inhibition of IkappaB kinase activation, this steroid blocked IkappaBalpha phosphorylation and degradation, thus suppressing p65 phosphorylation and nuclear translocation. NF-kappaB-dependent reporter gene transcription induced by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK was also blocked by guggulsterone but without affecting p65-mediated gene transcription. In addition, guggulsterone decreased the expression of gene products involved in anti-apoptosis (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), proliferation (cyclin D1 and c-Myc), and metastasis (MMP-9, COX-2, and VEGF); this correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents. Overall, our results indicate that guggulsterone suppresses NF-kappaB and NF-kappaB-regulated gene products, which may explain its anti-inflammatory activities.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Evaluation of the antineoplastic activity of guduchi (Tinospora cordifolia) in Ehrlich ascites carcinoma bearing mice.

              The anticancer activity of dichloromethane extract of guduchi [Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms. Family: Menispermaceae (TCE)] in the mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC mice receiving 25, 30, 40, 50 and 100 mg/kg, TCE showed a dose dependent elevation in tumor-free survival and a highest number of survivors were observed at 50 mg/kg TCE, which was considered as an optimum dose for its neoplastic action. The average survival time (AST) and median survival time (MST) for this dose were approximately 56 and 55 d, respectively when compared with 19 d of non-drug treated controls. Administration of 50 mg/kg TCE resulted in 100% long-term survivors (up to 90 d). An attempt was also made to evaluate the effectiveness of TCE in the various stages of tumor development, where 50 mg/kg TCE was administered intraperitoneally after 1, 3, 6, 9, 12 or 15 d of tumor inoculation and these days have been arbitrarily designated as stage I, II, III, IV or V, respectively for reasons of clarity. The greatest anticancer activity was recorded for stage I, II and III where number of long term survivors (LTS) was approximately 33, 25 and 17%, respectively. However, treatment of mice at stage IV and V did not increase LTS, despite an increase in AST and MST. The EAC mice receiving 50 mg/kg TCE showed a time dependent depletion in the glutathione (GSH) activity up to 12 h post-treatment and marginal elevation thereafter. This depletion in GSH was accompanied by a drastic elevation in lipid peroxidation (LPx) and a maximum elevation in LPx was observed at 6 h that declined gradually thereafter. TCE exerted cytotoxic effect on tumor cells by reducing the GSH concentration and increase in LPx simultaneously.
                Bookmark

                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                Nov-Dec 2012
                : 44
                : 6
                : 732-736
                Affiliations
                [1]Rajiv Gandhi University of Health Sciences, 4 th “T” Block, Jayanagar, Bangalore, Karnataka, India
                [1 ]R & D Center, The Himalaya Drug Company, Makali, Bangalore, Karnataka, India.
                Author notes
                Correspondence to: Dr. N. S. Prakash, E-mail: prakash.ns@ 123456himalayahealthcare.com
                Article
                IJPharm-44-732
                10.4103/0253-7613.103273
                3523501
                23248403
                bf9fa6a2-6897-4e5e-8e74-7ccffced33aa
                Copyright: © Indian Journal of Pharmacology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 August 2011
                : 27 June 2012
                : 31 August 2012
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                shatavarin iv,asparagus racemosus,anticancer,cytotoxicity,ehrlich ascites carcinoma

                Comments

                Comment on this article