Ding X, Staudinger JL. Induction of drug Metabolism by forskolin: the role of the pregnane X receptor and the protein kinase a signal transduction pathway. J Pharmacol Exp Ther. 2005;312(2):849-56. Http://www.ncbi.nlm.nih.gov/pubmed/.
An extract of the plant Coleus forskohlii has been used for centuries in Ayurvedic medicine to treat various diseases such as hypothyroidism, heart disease, and respiratory disorders. Additionally, complex herbal mixtures containing this extract are gaining popularity in United States for their putative "fat-burning" properties. The active ingredient in C. forskohlii extract is the diterpene compound forskolin. Forskolin is a widely used biochemical tool that activates adenyl cyclase, thereby increasing intracellular concentration of cAMP and thus actiVating the protein kinase A (PKA) signal transduction pathway. We show herein that both forskolin and its nonadenyl cyclase-actiVating analog 1,9 dideoxyforskolin induce CYP3A gene expression in primary hepatocytes by functioning as agonists of the pregnane X receptor (PXR). We show that activation of PKA signaling potentiates PXR-mediated induction of CYP3A gene expression in cultured hepatocytes and increases the strength of PXR-coactivator protein-protein interaction in cell-based assays. Kinase assays show that PXR can serve as a substrate for catalytically active PKA in vitro. Our data provide important insights into the molecular mechanism of both the PKA-dependent and -independent effects of forskolin on the expression of drug-metabolizing enzymes in liver. Finally, our data suggest that herbal therapy with C. forskohlii extract should be approached cautiously due to the potential for herb-drug interactions in patients on combination therapy.
Diwanay S, Chitre D, Patwardhan B. Immunoprotection by botanical drugs in cancer chemotherapy. J EthnoPharmacol. 2004 ;90(1):49-55. Http://www.ncbi.nlm.nih.gov/pubmed/.
Most of the synthetic chemotherapeutic agents available today are immunosuppressants, cytotoxic, and exert variety of side effects that are Particularly evident in cancer chemotherapy. Botanical based immunomodulators are often employed as supportive or adjuvant therapy to overcome the undesired effects of cytotoxic chemotherapeutic agents and to restore normal health. Total extract, polar and non-polar extracts, and their formulations, prepared from medicinal plants mentioned in Ayurveda, namely, Withania somnifera (Linn Dunal) (Solanaceae), Tinospora cordifolia (Miers) (Menispermaceae), and Asparagus racemosus (Willd.)(Liliaceae),exhibited various immunoPharmacological activities in cyclophosphamide (CP)-treated mouse ascitic sarcoma. Treatment of ascitic sarcoma-bearing mice with a formulation of total extracts of Withania somnifera and Tinospora cordifolia (80:20) and alkaloid-free polar fraction of Withania somnifera resulted in protection towards CP-induced myelo- and immunoprotection as evident by significant increase in white cell counts and hemagglutinating and hemolytic antibody titers. Treatment with these candidate drugs will be important in development of supportive treatment with cancer chemotherapy.
Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN. Comparative antioxidant and anti-inflammatory effects of -gingerol, -gingerol, -gingerol and -shogaol. J EthnoPharmacol. 2010;127(2):515-20. Http://www.ncbi.nlm.nih.gov/pubmed/.
Zingiber officinale Rosc. (Zingiberaceae) has been traditionally used in Ayurvedic, Chinese and Tibb-Unani herbal medicines for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. Although gingerols and shogaols are the major bioactive compounds present in Zingiber officinale, their molecular mechanisms of actions and the relationship between their structural features and the activity have not been well studied.
AIM OF THE STUDY:
The aim of the present study was to examine and compare the antioxidant and anti-inflammatory activities of gingerols and their natural analogues to determine their structure-activity relationship and molecular mechanisms.
MATERIALS AND METHODS:
The in vitro activities of the compounds -gingerol, -gingerol, -gingerol and -shogaol were evaluated for scavenging of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibition of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), inhibition of lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells.
In the antioxidant activity assay, -gingerol, -gingerol, -gingerol and -shogaol exhibited substantial scavenging activities with IC(50) values of 26.3, 19.47, 10.47 and 8.05 microM against DPPH radical, IC(50) values of 4.05, 2.5, 1.68 and 0.85 microM against superoxide radical and IC(50) values of 4.62, 1.97, 1.35 and 0.72 microM against hydroxyl radical, respectively. The free radical scavenging activity of these compounds also enhanced with increasing concentration (P<0.05). On the other hand, all the compounds at a concentration of 6 microM have significantly inhibited (P<0.05) f-MLP-stimulated oxidative burst in PMN. In addition, production of inflammatory mediators (NO and PGE(2)) has been inhibited significantly (P<0.05) and dose-dependently. CONCLUSIONS: 6-Shogaol has exhibited the most potent antioxidant and anti-inflammatory properties which can be attributed to the presence of alpha,beta-unsaturated ketone moiety. The carbon chain length has also played a significant role in making 10-gingerol as the most potent among all the gingerols. This study justifies the use of dry ginger in traditional systems of medicine.
Dwivedi C, Agrawal P, Natarajan K, Sharma H. Antioxidant and protective effects of Amrit Nectar tablets on adriamycin- and cisplatin-induced toxicities. J Altern Complement Med. 2005;11(1):143-8. Http://www.ncbi.nlm.nih.gov/pubmed/.
Maharishi herbal food supplements have been shown to inhibit the growth of mammary tumors and reduce free radical-mediated injuries. The purpose of this investigation is to evaluate the effects of aqueous and alcoholic extracts of Amrit Nectar tablets on rat liver microsomal lipid peroxidation and compare to other antioxidants. The protective effects of dietary Amrit Nectar tablets (MA-7; containing 38 herbs) on cisplatin-induced changes in glutathione (GSH) and glutathione-S-transferase (GST) activity in rat liver and kidney, and Adriamycin (Pharmacia S.p.A, Milan, Italy)-induced mortalities in mice were also investigated.
Both aqueous and alcoholic extracts of MA-7 were more potent than other antioxidants tested under our experimental conditions. Adriamycin (15 mg/kg, intraperitoneally) caused 60% mortality during the period of 4 weeks in CDF1 mice. Dietary MA-7 (0.7%) treatment decreased the mortality to 20%. Dietary MA-7 (0.7%) supplementation with cisplatin treatment reversed the effects of cisplatin on liver and kidney GSH and GST activity. CONCLUSIONS: These results indicate that MA-7 is a powerful antioxidant. MA-7 supplementation with Adriamycin and cisplatin treatment may protect against their toxicities.
Farag NH, Mills PJ. A randomised-controlled trial of the effects of a traditional herbal supplement on sleep onset insomnia. Complement Ther Med. 2003;11(4):223-5. Http://www.ncbi.nlm.nih.gov/pubmed/.
To study the effectiveness and safety of a traditional herbal supplement used for sleep onset insomnia.
A double-blind, randomized, placebo-controlled, cross-over study.
A total of 25 healthy volunteers (20-65 years of age) suffering from sleep onset insomnia were recruited from the general population.
A traditional Ayurvedic supplement formulated to reduce sleep onset insomnia. MAIN OUTCOME MEASURE: Sleep latency.
The supplement led to a statistically significant decrease in reported sleep latency of 16.72 min (S.D.=44.8) as compared to placebo (P=0.003). There were no self-reported side effects.
The findings suggest that traditional herbal supplements may be of significant benefit to patients suffering from sleep onset insomnia while avoiding the negative side effects of commonly prescribed hypnotics.
Flammang AM, Erexson GL, Mecchi MS, Murli H. Genotoxicity testing of a Salacia oblonga extract. Food Chem Toxicol. 2006;44(11):1868-74.Http://www.ncbi.nlm.nih.gov/pubmed/.
Salacia oblonga has been used for thousands of years in Ayurvedic medicine for the oral treatment of diabetes. The root extract has been shown to inhibit the activity of intestinal alpha-glucosidases, therefore S. oblonga holds potential as a natural method to mitigate the blood glucose response for people with diabetes. As part of a safety evaluation of novel ingredients for use in blood glucose control, the potential genotoxicity of a S. oblonga root extract (SOE) was evaluated using the standard battery of tests (reverse mutation assay; chromosomal aberrations assay; mouse micronucleus assay) recommended by US Food and Drug Administration (FDA) for food ingredients. SOE was determined not to be genotoxic under the conditions of the reverse mutation assay and mouse micronucleus assay, and weakly positive for the chromosomal aberrations assay. A reproducible, although weak, positive chromosomal aberrations response in human lymphocytes is of concern and further toxicity research is recommended. Use of SOE is presently expected to be safe, as anticipated intake is small compared to the doses administered in the genotoxicity assays and may, after further toxicity research, may prove be a useful ingredient in foodstuffs.
Funk JL, Frye JB, Oyarzo JN, Timmermann BN. Comparative effects of two gingerol-containing Zingiber officinale extracts on experimental rheumatoid arthritis. J Nat Prod. 2009;72(3):403-7. Http://www.ncbi.nlm.nih.gov/pubmed/.
Ginger (Zingiber officinale) supplements are being promoted for arthritis treatment in western societies on the basis of ginger's traditional use as an anti-inflammatory in Chinese and Ayurvedic medicine. However, scientific evidence of ginger's antiarthritic effects is sparse, and its bioactive joint-protective components have not been identified. Therefore, the ability of a well-characterized crude ginger extract to inhibit joint swelling in an animal model of rheumatoid arthritis, streptococcal cell wall-induced arthritis, was compared to that of a fraction containing only gingerols and their deriVatives. Both extracts were efficacious in preventing joint inflammation. However, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content) in preventing both joint inflammation and destruction. In conclusion, these data document a very significant joint-protective effect of these ginger samples and suggest that nongingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols.
Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.
Galal KM, Khaled Z, Mourad AM. Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer. Indian J Cancer.2011;48:47-54.Http://www.indianjcancer.com/.
Background: The relationship of epidermal growth factor receptors (EGFR) pathway, such as PI3K, K-ras, and B-raf, with response to EGFR-targeted antibodies is less well studied. Aim: To assess sorafenib with cetuximab in treating metastatic colorectal cancer. Settings and Design: Thirty-five patients with metastatic colorectal cancer were randomized to receive cetuximab with or without oral sorafenib. Patients and Methods: Patients received cetuximab IV weekly for four weeks and oral sorafenib twice daily on days 1 - 28, with recycling every four weeks. The primary end point was the response rate (pArtial and complete), while the secondary end points were the adverse effects, time to progression and overall survival. Statistical Analysis was made using the Statistical Product and Service Solutions, using SPSS 10.0, with estimation of both time to progression and overall survival time by the Kaplan-Meier method and comparing the two groups with the use of a log-rank test. Results: PArtial response was higher in cetuximab-sorafenib (EN), which constituted 33.3% compared to 17.6% in the cetuximab group (P = 0.44). Progression-free survival had a statistically higher significant difference in wild K-ras compared to mutant K-ras cases (P = .0001). Median overall survival was seven and five months in the (EN) and (E) groups respectively (P = 0.49). Conclusion: K-ras and B-raf was a predictor of response, so genotyping of tumors was needed for defining the patient population that was likely to benefit from the targeted therapy. A combination of therapy that simultaneously targets K-ras and B-raf could be a useful approach to increase the number of patients who may benefit from anti-EGFR therapy.
Ganguly T, Badheka LP, Sainis KB. Immunomodulatory effect of Tylophora indica on Con A induced lymphoproliferation. Phytomedicine. 2001;8(6):431-7. Http://www.ncbi.nlm.nih.gov/pubmed/.
Our preliminary studies with tylophora alkaloids had shown that they inhibit cellular immune responses like contact sensitivity to dinitro-flurobenzene and delayed hypersensitivity to sheep red blood cells, in vivo. Investigations were hence carried out to determine the cellular targets of tylophora alkaloids in in vitro systems. Con A induced proliferation of splenocytes was used as a model system to study the effect of the alkaloids on cellular immune responses. The alkaloid mixture was found to inhibit proliferation of splenocytes at higher concentrations and augment the same at lower concentrations. Both macrophages and T cells were found to be vulnerable to tylophora alkaloids. The alkaloid mixture suppressed IL-2 production in Con A stimulated splenocytes at the inhibitory or higher concentrations and enhanced production at the lower concentrations. IL-1 production by activated macrophages on the contrary was doubled in the presence of inhibitory concentrations of tylophora. These studies indicate that tylophora alkaloids have a concentration dependent biphasic effect on Con A induced mitogenesis. At lower concentrations they augment Con A induced lymphoproliferation by enhancing IL-2 production. Inhibition of proliferation at higher concentrations of the alkaloid is due to inhibition of IL-2 production and activation of macrophages, which have a cytostatic effect.
Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809.Http://www.ncbi.nlm.nih.gov/pubmed/.
Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion Molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, Psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".
Goel RK, Prabha T, Kumar MM, Dorababu M, Prakash, Singh G. Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine. Indian J Exp Biol. 2006;44(7):570-3.Http://www.ncbi.nlm.nih.gov/pubmed/.
Asparagus racemosus (AR) is a herb used as a Rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.
Gopi S, Setty OH. Beneficial effect of the administration of Hemidesmus indicus against bromobenzene induced oxidative stress in rat liver mitochondria. J EthnoPharmacol. 2010;127(1):200-3.Http://www.ncbi.nlm.nih.gov/pubmed/.
AIM OF THE STUDY:
To study the beneficial effect of the prior administration of an aqueous extract of Hemidesmus indicus against bromobenzene induced oxidative damage in rat liver mitochondria.
MATERIALS AND METHODS:
Oxidative stress was induced in rats with bromobenzene (10 mmol/kg body wt.). The rate of respiration, P/O ratios, lipid peroxides, protein carbonyls and sulphydryls were studied.
When the rats were administered with bromobenzene, the rate of respiration was decreased significantly and the P/O ratio was completely abolished. There was a significant increase on the levels of lipid peroxide and protein carbonyl and a significant decrease on total sulphydryl groups when compared with control. Administration of rats with an aqueous extract (100mg/kg) prior to bromobenzene administration showed significant beneficial effects like, stimulation in respiration, prevented the rise in lipid peroxides and protein carbonyls, increased the level of sulphydryl groups back to control level. Administration of vitamin E could not reverse as effectively as Hemidesmus indicus.
This study demonstrates a good protective effect of Hemidesmus indicus against the bromobenzene induced oxidative stress.
Govindarajan R, Vijayakumar M, Rao ChV, Pushpangadan P, Asare-Anane Persaud S, Jones P, Houghton PJ. Antidiabetic activity of Croton klozchianus in rats and direct stimulation of insulin secretion in-vitro. J Pharm Pharmacol.2008;60(3):371-6.Http://www.ncbi.nlm.nih.gov/pubmed/.
Croton klozchianus is a relatively uninvestigated species with no Pharmacological or phytochemical reports available, although it has been used clinically by Ayurvedic physicians to treat diabetes. We have investigated this use by studying the insulin secretion and antidiabetic activity of C. klozchianus. Treatment of diabetic rats with aerial parts of C. klozchianus extract (CK, 100 and 300 mg kg(-1) body weight) for three weeks showed significant reduction in blood glucose (45.8% after 14 days for 300 mg kg(-1)). C. klozchianus extract caused a significant concentration-dependent increase in insulin secretion (8-fold at 2 mg mL(-1) for cells challenged with 20 mM glucose) from MIN6 cells grown as monolayers and as pseudoislets, indicating that the antidiabetic activity may have been as a result of increased insulin secretion. It also had a role on the lipid profile of the rats by causing reduction in cholesterol and triglycerides and increasing high density lipoprotein significantly. The results obtained gave some scientific support to the traditional use of the plant as a treatment for diabetes.
Gupta A, Mishra A K, Bansal P, Kumar S, Sannd R, Gupta V, Goyal B M, Singh A K, Kumar A, Antilaprotic Potential of Ethnomedicinal Herbs: A Review. Drug Invention Today. 2010;2(3):191-193
The World Health Organization estimates that about 80% of the population of most developing countries relies on herbal medicines for their primary health care needs. Presently there are many medicinal herbs under investigation for their potential health protection. Among the products under investigation are commonly consumed products like vegetables, fruits and condiments expected to protect health and possess disease inhibiting properties like leprosy which caused by Mycobacterium leprae. This review therefore attempts to bridge the existing literature and modern research and offers immense scope for researchers engaged in validation of the traditional claims and development of safe, effective and globally accepted herbal drugs for treatment of leprosy.
Gupta R, Singhal S, Goyle A, Sharma VN. Antioxidant and hypocholesterolaemic effects of Terminalia Arjuna tree-bark powder: a randomised placebo-controlled trial. J Assoc Physicians India. 2001;49:231-5.Http://www.ncbi.nlm.nih.gov/pubmed/.
To evaluate the antioxidant and hypocholesterolaemic effects of Terminalia Arjuna tree bark (a popular cardiotonic substance in Indian pharmacopoeia) and to compare it with a known antioxidant, vitamin E, we performed a randomized controlled trial.