The gastric ulcer protective effect of boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats

Aim of the study is to evaluate the anti-ulcer efficacy of the boswellic acids (BA), a triterpenoid known as antiinflammatory/anti-arthritic agent, which is in clinical use. The reason for the study is that, the known non-steroidal anti-inflammatory drugs (NSAIDs) are full of side effects especially ulceration which is at the top. BA, although, used as an anti-arthritic agent yet it is not only devoid of ulcer production but protective also. The activity evaluation was done by the following universally accepted animal models viz., pyloric ligation, ethanol–HCl, acetylsalicylic acid,indomethacin and cold restrained stress-induced ulceration in rats. Results of the present study revealed that BA possess a dose dependent antiulcer effect against different experimental models. It showed different degree of inhibition of the ulcer score towards different ulcerogenic agents. The ulcer score against various ulcer inducing agents viz.,pyloric ligation, ethanol/HCl, (acute and chronic) acetylsalicylic acid, indomethacin and cold restraint stress, was inhibited by 39%, 38%, 51%, 31%, 37% and 42% respectively at 250 mg/kg. From the data it is concluded that BA inhibited ulcer production non-specifically in all the experimental models, whereby, it is not possible to propose a single specific mechanism. Nevertheless it is possible that BA might be acting by increasing the gastric mucosal resistance and local synthesis of cytoprotective prostaglandins and inhibiting the leukotriene synthesis

Anti-­Histaminic Potential of the Fractions from Hedranthera Barteri [(Hook F.) Pichon] Root in Laboratory Rodents

Hedranthera barteri L. (HB) is used in the treatment of painful conditions and oedema amongst its folkloric use. The hexane and ethyl acetate fractions of the root of H. barteri were investigated for anti-nociceptive and antiinflammatory properties and probable mechanism of action. Hot plate, tail flick, formalin-induced oedema and acetic acidinduced writhing tests were employed to investigate the anti-nociceptive activity while the anti-inflammatory activity was investigated using carrageenan-induced paw oedema. Anti-histaminic potential of HB root extracts on the rat peritoneal mast cells (RPMCs) was explored through spectrofluorometric method. The root was screened for its phytochemical components. The HB root contains alkaloids, cardenolides and saponins. HXHBR exhibited higher anti-inflammatory potentials (P<0.001). HXHBR dose-dependently (P<0.01) reduced the histamine release from the rat peritoneal mast cells which is comparable with a standard anti-histaminic drug, ketotifen. These results showed that EAHBR and HXHBR possess anti-nociceptive and anti-inflammatory activities, and suggested its mechanism of action through the inhibition of histamine, an inflammatory mediator, usually released during the early phase of allergic responses and chronic phase of inflammatory pain. Flavonoids, alkaloids and/or saponins present in HB root may be responsible for its anti-nociceptive and anti-inflammatory properties

Boswellic acids: A leukotriene inhibitor also effective through topical application in inflammatory disorders

Boswellic acids (BA), a natural mixture isolated from oleo gum resin of Boswellia serrata comprised of four major pentacyclic triterpene acids: b-boswellic acid (the most abundant), 3-acteyl-b-boswellic acid, 11-keto-b-boswellic acid,and 3-acetyl-11-keto-b-boswellic acid, is reported to be effective as anti-inflammatory, immunomodulatory, antitumor,anti-asthmatic and in Chron’s disease. It inhibits pro-inflammatory mediators in the body, specifically leukotrienes via inhibition of 5-lipoxygenase, the key enzyme of leukotriene synthesis, is the scientifically proved mechanism for its anti-inflammatory/anti-arthritic activity. All previous work on BA for its biological activity has been done through the systemic application but no pre-clinical data reported for its anti-inflammatory activity by topical application. We here by report anti-inflammatory activity of BA through this route by applying different acute and chronic models of inflammation i.e., arachidonic acid and croton oil-induced mouse ear edema, carrageenan-induced rats paw edema and adjuvant-induced developing arthritis in rats. The results of the study revealed that the effect observed through this route is in accordance to the study conducted with the systemic route, thus establishing that BA when used through topical application is as effective as through the systemic route

Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC 13qTOF-MS: Evidence that PA-1 enhances the oral bioavailability of etoposide in mice

In the present investigation, a UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of etoposide and a piperine analogue, namely, 4-ethyl 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1). The analytes were separated on a reverse phase C18 column using methanol-water (72:28, v/v) mobile phase with a flow rate of 250 microL/min. The qTOF-MS was operated under multiple reaction monitoring mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions for etoposide and PA-1 were at m/z 185.1350 and 164.1581, respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. The total run time was 6 min and the elution of etoposide and PA-1 occurred at 1.24 and 2.84 min, respectively. The calibration curves of etoposide as well as PA-1 were linear over the concentration range of 2-1000 ng/mL (r(2), 0.9829), and 1-1000 ng/mL (r(2), 0.9989), respectively. For etoposide intra-assay and inter-assay accuracy in terms of % bias was in between -7.65 to +6.26, and -7.83 to +5.99, respectively. For PA-1 intra-assay and inter-assay accuracy in terms of % bias was in between -7.01 to +9.10, and -7.36 to +6.71, respectively. The lower limit of quantitation for etoposide and PA-1 were 2.0 and 1.0 ng/mL, respectively. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). The method was used for a pharmacokinetic study which showed that PA-1 enhanced the oral bioavailability of etoposide in mice by 2.32-fold

Possible role of macrophages induced by an irridoid glycoside (RLJ-NE-299A) in host defense mechanism

In order to explore the possible role of macrophages and other necessary immune competent (T and B) cells in the modulation of immune responses, an attempt was made to study the immunomodulatory effect of an irridoid glycoside (RLJ-NE-299A) isolated from the roots of Picrorhiza kurroa. Both in vitro and in vivo studies were used to evaluate the effect of RLJ-NE-299A on humoral, cellular, and phagocytic activity of macrophages.The data obtained in the present study showed that RLJ-NE-299A significantly increased sheep red blood cell(SRBC) and induced antibody (IgM and IgG) titer and delayed type hypersensitivity (DTH) reaction in mice.Besides augmenting the humoral and cell-mediated immune response, it induced macrophage phagocytosis and stimulated cytokine-induced macrophage activation and nitric oxide (NO) production, which resulted in a high degree of protection against Candida albicans and Salmonella typhimurium infections. Flow cytometric analysis indicated the enhanced expression of co-stimulatory surface molecules CD80 and CD86. The ability of RLJ-NE-299A to upregulate these cell surface antigens involved in antigen presentation may provide an explanation for the increased T-cell mediated immunity involving macrophages. Taken together this in vitro and in vivo preclinical data suggests that RLJ-NE-299A acts as an effective immunomodulator specifically to improve macrophage function during infections. The effects of this agent on these cells at concentrations relevant to in vivo therapy support its immunopharmacologic application to modify cellular immunity

Anti-histaminic, anti-inflammatory and bronchorelaxant activities of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one

An immunopharmacological profile of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one(P-I) has been investigated using in vitro and in vivo models representing various features of Type I allergy. P-I prevented compound 48/80-mediated histamine release from rat peritoneal mast cells. A promising anti-inflammatory activity of P-I was evident in active paw anaphylaxis (mice)and carragenan-induced paw edema (rat). P-I inhibited eosonophil accumulation and eosinophil peroxidase activity in bronchoalveolar lavage fluid from ovalbumin challenged balb/c mice: in these animals blood levels of IL-5, and CD4+ T cells also remained attenuated. A promising bronchorelaxant effect of P-I was observed in histamine-contracted guinea pig tracheal chain via its antagonism to H1 receptor. These findings were compared with some known compounds(ketotifen, cetirizine and promethazine). The anti-histaminic, anti-inflammatory and bronchorelaxant activities of P-I has been discussed in context with its potential profile as an anti-allergic and anti-asthmatic agent

A novel sarsasapogenin glycoside from Asparagus racemosus elicits protective immune responses against HBsAg

The aim of the present investigation was to evaluate the adjuvant potential of a novel sarsasapogenin glycoside (immunoside) isolated from Asparagus racemosus in combination with hepatitis B surface antigen(HBsAg). Various in vitro and animal derived protocols were used to determine the response of immunoside adjuvanted with HBsAg and the results were compared with alum adjuvanted with HBsAg.Several biomarkers such as antibody titre (IgG, IgG1/IgG2a) were measured in mice sera. Cell proliferation, cytokines (IL-2, IFN-� and IL-4), and lymphocyte sub-populations (CD4/CD8, CD3 and CD19)were determined in splenocytes from mice administered subcutaneously with test substances. In these cells CD4/CD8 derived IFN-� release was also determined. Macrophage preparations were used for the determination of IL-12, IFN-� and nitrite content. Seroconversion potential was compared with a standard vaccine. Acute safety evaluation of immunoside was done in mice. Effect of immunoside on red blood cell haemolysis was determined. The results have suggested that immunoside potentially enhanced anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner

Simultaneous high-performance liquid chromatographic determination of Cedrus deodara active constituents and their pharmacokinetic profile in mice

A specific and sensitive high-performance liquid chromatographic (HPLC) method with photodiode-array (PDA) ultraviolet detection was developed for the simultaneous determination of three bioactive constituents of Cedrus deodara namely wikstromol, matairesinol and dibenzylbutyrolactol in mouse plasma. In solid-phase extraction (SPE) these constituents were successfully separated using a C18 column by isocratic elution using acetonitrile:water containing hexanesulphonic acid, 32:68 (v/v). The flow rate was set at 1 ml/min and detector wavelength at 225 nm. Good linearity (r2 > 0.999) was observed over the studied range of 0.015–5.0 �g/ml for wikstromol and 0.030–5.0 �g/ml for matairesinol and dibenzylbutyrolactol.The CV values of intra-day precision for wikstromol, matairesinol and dibenzylbutyrolactol were in between 1.8–6.9, 1.7–4.9 and 1.6–4.2% and values of inter-day precision were in between 10.4–12.2, 9.7–11 and 10–11.2%, respectively. The extraction recoveries at low to high concentration were greater than 98, 83 and 87% for each analyte, respectively. The LOQ for wikstromol was 0.015 �g/ml and for both matairesinol and dibenzylbutyrolactol it was 0.030 �g/ml. The developed method was used to determine the pharmacokinetics of the three analytes in mice after intraperitoneal administration of CD-3

Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb

Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as ‘‘Kacipn Fatimah”. Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women’s health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50 mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns