Mubashir H. Masoodi

Phytoconstituents and therapeutic uses of Rheum emodi wall. ex Meissn

Abstract Rhubarb (Rheum emodi, family Polygonaceae) has been traditionally used as diuretic, liver stimulant, purgative/cathartic, stomachic, anticholesterolaemic, antitumour, antiseptic and tonic. A number of anthraquinone derivatives including emodin, aloe-emodin, physcion, chrysophanol, rhein, emodin glycoside and chrysophanol glycoside occur as the main chemical constituents. In the past few years, new components such as sulfemodin 8-O-β-d-glucoside, revandchinone-1, revandchinone-2, revandchinone-3, revandchinone-4, 6-methyl-rhein and 6-methyl aloe-emodin have been reported from the same species. Anthraquinone derivatives show evidence of antifungal, anti-microbial, anti-Parkinson’s, anti-proliferative, immuno-enhancing, antiviral and antioxidant activities. This review covers published work on botany, chemistry and therapeutic uses of different components from rhubarb.

Antihyperlipidemic and Antioxidant Potential of Paeonia emodi Royle against High-Fat Diet Induced Oxidative Stress

The present study was intended to evaluate the effects of Paeonia emodi rhizome extracts on serum triglycerides (TGs), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), atherogenic index (AI), superoxide dismutase (SOD), and glutathione peroxidase (GPx). The plant was extensively examined for its in vitro antioxidant activity, and the preliminary phytochemical screening was carried out using standard protocols. Male Wistar rats were induced with hyperlipidemia using high-fat diet and were treated orally with hydroalcoholic and aqueous extracts at the dose of 200 mg/kg bw for 30 days. TGs, TC, LDL-c, and AI were significantly reduced while HDL-c, SOD, and GPx levels rose to a considerable extent. After subjecting to acute toxicity testing, the extracts were found to be safe. The observations suggest antihyperlipidemic and antioxidant potential of P. emodi in high-fat diet induced hyperlipidemic/oxidative stressed rats.

Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS

The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt) from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF) induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg) intraperitoneal (i.p.) injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight) distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS) were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids.

Lead finding from whole plant of Marrubium vulgare L. with Hepatoprotective Potentials through in silico methods

Abstract Objective In the present study an attempt has been made to study the antihepatotoxic activity of active compounds in this plant through in silico methods. Methods We have taken 12 compounds form this plant. All the compounds were further subjected to molecular propertied prediction and drug likeness by Molinspiration and found in compliance with Lipinskis rule of five. Biochemical parameters like SGOT and SGPT were determined by Reitman and Frankel, ALP by Kind and King, TP by reported methods of Wooton. Results All the compounds were showed expected similar bioactivity especially in case of enzyme inhibition. Compound Vulgarin showed no violation with good drug likeness score and biological activity as compare to standard drug Silibinin. Vulgarin exhibited a significant antihepatotoxic activity by reducing the elevated levels of serum enzymes such as serum glutamate oxaloacetate transaminase (SGOT) serum glutamate pyruvate oxaloacetate transaminase (SGPT) and alkaline phosphatase (ALP) while the total protein (TP) levels were increased when compared with standard drug silymarin against CCl4-induced toxicity in Wistar rats. These biochemical observations were also supplemented by histopathological examinations of the liver sections. Conclusions We found that Vulgarin one of the twelve compounds is showed better drug likeness and biological activity against Silibinin. So this particular compound can be taken as lead compound for further drug discovery for hepatotoxic activity.

Naringenin (4,5,7-trihydroxyflavanone) suppresses the development of precancerous lesions via controlling hyperproliferation and inflammation in the colon of Wistar rats

Colon cancer is a world‐wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7‐trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chineses traditional medicine because of its exceptional pharmacological properties and non‐toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2‐dimethyhydrazine (DMH)‐induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3‐5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2‐4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH‐induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF‐κB‐p65, COX‐2, i‐NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF‐α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH‐induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin.

Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) protects against alloxan-induced diabetes via alleviation of oxidative stress and inflammation: Probable role of NF-kB activation

Diabetes is considered as the most common metabolic disease affecting millions of people all around the world. Use of natural herbal medicines can be effective in treating diabetes. Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) a polyphenolic alkanone extracted from ginger has a broad spectrum of pharmacological properties and thus can be used as a promising candidate against various ailments. In the current study we aimed at demonstrating the protective effect of zingerone against diabetes mellitus and elucidating its possible mechanism. Five groups of animals (I-V) were made with ten animals each. Group I (control) was given normal saline orally. Group II (diabetic positive control) was given alloxan at the dose rate of 100 mg/kg bwt once. Group III and IV was given alloxan once at the dose rate of 100 mg/kg bwt. and received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg bwt respectively daily for 21 days. Group V was given alloxan at the dose of 100 mg/kg bwt. and was treated with standard drug glibenclamide at the dose rate of 4.5 mg/kg bwt. daily for 21 days. According to our findings we confirmed that zingerone restrained the alloxan induced oxidative stress by increasing the activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and reducing the peroxidative damage. We also confirmed that zingerone suppressed the level of redox sensitive transcription factor NFκB and downregulated other downstream inflammatory cytokines like interleukins (IL1-β IL-2, IL-6) and tumor necrosis factor alpha (TNF-α). Moreover, the experimental findings suggested that zingerone improved the insulin levels. Taken together our results indicated that zingerone effectively ameliorated the diabetes induced complications which provide a strong theoretical basis for zingerone to be used clinically for treatment of diabetes.

Evaluation of antioxidant activity of Portulaca oleracea Linn. from Kashmir Himalaya

T annual incidence of urolithiasis in industrialized regions is considered to be 1,500-2,000 cases per millions with reoccurrence rate of 75% in 20 years. There is no effective management therapy for renal calculi. Allopathic and herbal therapies havetheir inherent limitations and side-effects. Bergenia ligulata has been used since ancient time in many herbal compositions and it is major component of Cystone® (Himalaya, herbal healthcare) for treating kidney stones. The present work has been designed to study the anti-lithiatic potential of B. ligulata, isolation of the potent metabolite(s) and its mechanism of action. Commercially available dried rhizomes of B. ligulata were powdered and subjected to activity guided fractionation using in vitro calcium oxalate crystal growth inhibition assay. Further, rat hyperoxaluric model was used to assess anti-lithiatic ability in vivo. The isolated fractions showed anti-calcifying activity in vitro. The sequential isolation of the potent fraction led to the purification of the most active molecule. The metabolite was eventually characterized as bergenin employing LC-MS, NMR, FTIR and UV spectroscopy. Bergenin was found to be effective in reducing oxidative stressmarkers like malondialdehyde (187% in diseased vs. 20% in treated) and elevating reduced glutathione levels (-46% in diseased vs. -15% in treated). It exhibited anti-lithiatic activityas assessed by measuring the activity of lactate dehydrogenase and alkaline phosphatase in serum samples. The creatinine clearance was also normalized with bergenin treatment in rat hyperoxaluric model. The present study provides significant evidence in the effectiveness of bergenin in treating and managing renal calculi.D mellitus is a metabolic disorder constituting a major health concern today whose prevalence has continuously increased in the world. The aim of this study is to evaluate the anti-diabetic potential of methanolic extract of Hyoscyamus albus (HAMeOH) in diabetic rats. Hyoscyamus albus (Solanaceae) is an herbal medicine traditionally applied as a parasympatholytic and nervous sedative. The oral glucose tolerance test (OGTT) was carried out by administering glucose (2 g/kg, b.w), to non-diabetic rats treated with HAMeOH at oral doses 100 and 200 mg/kg, b.w and glibenclamide 5 mg/kg. Also, Streptozotocin-induced diabetic rats, these diabetic rats were administered (100 and 200 mg/Kg b.w ) and standard drugs glibenclamide was given to rats for 30 days. The oral administration of both doses of HAMeOH significantly reduced the levels of blood glucose and glycosylated hemoglobin in diabetic rats. Determination of plasma insulin levels revealed the insulin stimulating action of the leaves extract. It is concluded that HAMeOH have significant anti-diabetic activity.Grewia nervosa (Lour) Panighrahi, belonging to the family Malvaceae s.l. is widely distributed along the Western Ghats of India. Although it has been commonly used in traditional medicine, the medicinal properties have not been scientifically evaluated. Phytochemical analysis established the presence of phenolic compounds, tannins, alkaloids and saponins in leaves. The aqueous and methanol extracts from leaves and bark of G. nervosa were investigated for medicinal properties using in vitro assays. The methanol extract of leaves demonstrated 97.5% inhibition of α-amylase activity. Additionally, the methanol extract of leaves also demonstrated antioxidant activity (5.41± 0.23 mmol/g, dw) that was higher compared to aqueous extract (3.32±0.45 mmol/g, dw). Further the methanol extract of bark exhibited anti-lipoxygenase activity indicative of its potential to control inflammatory activity. These results suggest that Grewia nervosa would be a potential source for treatment of diabetes and its associated complications such as oxidative stress and inflammationC herbs (Asteraceae) are extensively used as food additives and in folk medicine. Anti-cancer, anti-human immunodeficiency virus type 1 (HIV-1), anti-inflammatory, antinociceptive and antiproliferative activities as well as antioxidant effects have been reported for Chrysanthemum species. We report the isolation and identification of flavonoids and new and known terpenoids from the endemic species, C. macrocarpum and C. deserticolum “guertoufa”, used in Algerian Sahara as tea drinks and in “couscous” and soups “Chorba”. Structures of the isolated compounds were established by 1-D and 2-D homo and hetero-nuclear NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY), mass spectrometry, UV and comparison with literature data. C. deserticolum extracts were tested by four methods to identify the antioxidant activity namely, ABTS•+, DPPH• scavenging, CUPRAC and ferrous-ions chelating activity methods. The in vitro anticholinesterase activity was achieved by the use of the basic enzymes that occur in causing Alzheimer’s disease: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Anti-inflammatory, antinociceptive, antiproliferative and antioxidant activities of C. macrocarpum extracts and isolated compounds are also reported here.T practice of traditional medicine for the control of fertility in most parts of India is based on the uses of plant medicines for many years. The aim of the present study was to evaluate the post coital antifertility activity of different varieties of Curcuma longa and underlying mechanism thereof. The effects of n-hexane, chloroform and acetone fraction of hydroalcoholic extract of three different varieties i.e. Salem, Krishna and Rajapore of Curcuma longa rhizomes were studied at three different doses to evaluate their antifertility, early abortifacient, antiovulatory activities and underlying mechanism thereof. Acute toxicity and thin layer chromatographic studies of same were also carried out. All varieties found to have significant antifertility activity (p<0.01). The n-hexane fraction of all varieties showed anti-implantation activity at the dose of 150 mg/kg weight whereas chloroform and acetone fraction of all varieties exhibited 100% reduction in pregnancy at the dose of 300 mg/kg body weight. Antifertility activity of test drugs was found through its antizygotic mechanism whereas all test drugs devoid of any antiovulatory and early abortifacient activity at all doses.M charantia (MC) fruits have previously been reported to reduce blood glucose in laboratory animals and human subjects with diabetes. Increase in insulin secretion is one of the chief mechanisms of antidiabetic action of MC extracts or their purified molecules. In present study the effect of aqueous extracts of MC (AEMC) was studied on insulin secretion in isolated pancreatic islets from normal Wistar rats with an attempt to evaluate the mechanism of action. Islets were incubated in HBBS buffer containing 3.3 or 16.7mM glucose, and AEMC, diazoxide, nimodipine and calphostin C, alone and in combinations. Release of insulin in external media was measured by ELISA. Cytotoxicity studies, to assess the integrity of the islets cells, were carried out by trypan blue uptake and LDH release assay. Trypan blue gained access to 9.6 ± 1.2% cells and 8.3 ± 1.1% dead islet cells were observed in LDH release assay on AEMC exposure, suggesting that the extract was non-toxic at tested concentration. AEMC stimulated insulin secretion from the isolated islets at 3.3 and 16.7 mM glucose. The effect of AEMC was dose dependent. As loss of cell integrity was not observed on AEMC exposure, hence, alteration of membrane integrity as the possible mechanism of insulin release is ruled out by this study. Addition of dizoxide and nimodipine completely diminished glucose induced insulin secretion. AEMC induced insulin secretion at 16.7mM glucose was partially inhibited by dizoxide and nimodipine, however no reduction was observed at 3.3mM of glucose. No change in insulin secretion at basal level of 3.3 mM of glucose suggests that the phytochemicals of AEMC may not be binding to either KATP or Ca channels. Calphostin C significantly (p<0.01) reduced AEMC induced insulin production both at 3.3 mM and 16.7 mM. The finding suggests that PKC inducing activity of AEMC phytochemical/s may be responsible for its insulin secretagogues potential.Bioassay-guided fractionation of the CH2Cl2/MeOH extract of the Thai marine sponge Acanthodendrilla sp. resulted in the isolation of six bromotyrosine-derived alkaloids; aerothionin (1), homoaerothionin (2), 2-hydroxy-3,5-dibromo,4methoxyphenylacetamide (3), 2,4-cyclohexadiene-1-acetamide-3,5-dibromo-1,6-dihydroxy-4-methoxy (4), 11-oxoaerothionin (5), and 11,19-dideoxyfistularin (6) . The structures of the isolated compounds were identified on the basis of detailed spectroscopic analysis. The compounds were tested for the acetylcholinesterase-inhibiting activity, and 3 showed the best acetylcholinesterase-inhibiting activity (92.0% at 0.1 mg/mL).T hepatoprotective activity of methanolic extract of bark of Ficus bengalensis against paracetamol and CCl4 induced liver damage was investigated. Treatment of rats with paracetamol and CCl4 produced a significant increase in the levels of serum glutamate pyruvate transaminase SGPT, serum glutamate oxaloacetate transaminase SGOT, alkaline phosphatase ALP, total and direct bilirubin. Rats pretreated with methanolic extract of barks of F. bengalensis 100 and 250 mg/kg body weight p.o. exhibited rise in the levels of these enzymes but it was significantly less as compared to those treated with paracetamol or CCl4 alone. The results of methanolic extract of F. bengalensis were comparable with the standard hepatoprotective agent silymarin 100 mg/kg. Maximum hepatoprotective effect was found to be at the dose of 250 mg/kg body weight in case of CCl4 induced hepatic damage while 500 mg/kg body weight in case of paracetamol induced hepatic damage. Obtained data suggest that methanolic extract of F. bengalensis bark possesses a potential antihepatotoxic activity.The medicinal quality of plants has been known and exploited by man for centuries. A large number of modern drugs have been isolated from traditional herbal plants[1]. Numerous secondary metabolites obtained from plants, with previously unknown pharmacological activities, have been extensively investigated as a source of medicinal agents[1,2]. The acceptance of traditional medicine as an alternative form of health care and the development of microbial resistance to the available antibiotics led to investigation on the antimicrobial activity of medicinal plants. The increasing failure of chemotherapeutics and antibiotic resistance exhibited by pathogenic agents has led to the screening of several PEER REVIEW ABSTRACTT genus of Phoebe of family Lauraceae is found the most abundance in Borneo and the Malaysian Peninsular. Phoebe tavoyana is locally known as ‘medang rungkoi.’ The woods of Phoebe species have the commercial values usually for housebuilding. As a wood of a good type soft to moderately hard, light, slightly colored than the hardwood used for carving and sculpture, paneling for doors altars wardrobes, carriages and ceiling. Phytochemical study on the leaves of Phoebe tavoyana (Meissn.) H.K.F. from Chebar Besar Reserved Forest, Kuala Kangsar, Perak, Malaysia has resulted the isolation of four known aporphines; laurolitsine (1), roemerine (2), laetanine (3), boldine (4) and one morphinandienone type, sebiferine (5). The structures of alkaloids were determined by spectroscopic analysis. This paper reports the antiplasmodial activity of three alkaloids from the leaves of Phoebe tavoyana (Lauraceae). The results showed that (1), (2) and (5) have shown potent inhibitory activity against the growth of Plasmodium falciparum 3D7 clone, with IC50 1.49, 0.89 and 2.76μg/mL respectively. No previous phytochemical investigation has been performed on this plant.Natural polysaccharides have been widely used because of their biocompatibility and biodegradabilityproperties. An attempt has been made to explore tamarind seed xyloglucan (TSX), a glucosaminoglycan polysaccharide extracted from the kernels of seeds of Tamarindus indica Linn., family Fabaceae for bimodal(immediate and controlled)drug release of multilayer tablet. Chemically TSX powder is highly branched carbohydrate polymer. High drug holding capacity of this polysaccharide was investigated for bimodal release.An in-house extracted TSX polysaccharide was characterized for swelling index, flow property, viscosity and compatibility with drug. Multilayer tablet was comprised of immediate release layer of tramadol hydrochloride (an analgesic agent), followed by tri-layer. This tri-layer consisted of upper and lower barrier layers of TSX and middle layer of drug granular matrix. Multilayer tablets were compressed based on 3 2 factorial design consideringconcentrations of matrix and barrier TSX layers as independent variables. Immediate release layer released the drug within 90 min in acidic media, revealing the retarded action showed bypolysaccharide layer attached to this layer. Granules of matrix layer were prepared by wet granulation technology.Multiplayer tablet of TSX was evaluated for hardness, thickness and drug content. Dissolution test in presence of rat caecal content was found to control the drug release rate for more than 9h. Stability studies confirmed the stable formulation. Thus, this study suggested that inexpensiveand abundantly available natural TSX can act as a potential polymer for bimodal releaseof a multilayer tablet.