Immunomodulatory and anti-inflammatory effects of Semecarpus anacardium LINN. Nut milk extract in experimental inflammatory conditions

Immunomodulatory effects of Semecarpus anacardium LINN. nut milk extract (SA) were investigated in adjuvant induced arthritis by studying the alterations in humoral and cell mediated immune responses and also the anti-inflammatory effects by evaluating the changes in paw edema, tumour necrosis factor (TNF-alpha), nitric oxide and myeloperoxidase activities. Pharmacological studies were also conducted with SA and indomethacin on experimental animals for evaluating the anti-inflammatory, analgesic, antipyretic and ulcerogenic activities. The alterations in the humoral and cell mediated immunity were significantly reverted back to near normal levels on treatment with SA. The drug significantly reduced the elevation in the paw edema, TNF-alpha, nitric oxide and myeloperoxidase levels when compared with adjuvant induced arthritic animals, which shows the anti-inflammatory activity of the drug. SA showed strong anti-inflammatory effects in xylene-induced ear edema and formalin-induced inflammation. In analgesic test, the extract elicited a potential activity on both acetic acid-induced writhing response as well as hot plate test showing its central and peripheral mediated action. The drug also elicited antipyretic action in yeast-induced hyperemia in rats. In addition, the extract did not produce any ulceration on gastric mucosa during ulcerogenic test and did not produce any serious adverse effects. All these effects are nearly similar to the activities of indomethacin except the ulceration where indomethacin produced significant ulceration. From this study, the protective immunological and pharmacological role of SA is demonstrated.     

Evaluation of antioxidant effect of Semecarpus anacardium Linn. nut extract on the components of immune system in adjuvant arthritis

The effect of Semecarpus anacardium Linn. nut extract (SA) on the level of Lipid peroxides (LPO) and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the lymphocytes and lymphoid organs, namely spleen and thymus of adjuvant induced arthritic rats, were investigated. The results were compared with normal and untreated arthritic rats. The levels of reactive oxygen species (ROS), namely Hydroxy radical, Superoxide radical, and H2O2 were also measured in spleen, thymus, and lymphocytes of control and experimental animals. Biochemical markers of inflammation namely C-reactive protein (CRP) level and Erythrocyte sedimentation rate (ESR) were determined. Anti-arthritic profile was evaluated from the changes in the paw edema and arthritic scores of arthritic and drug-treated rats. A significant increase in the level of LPO, ROS and decreased levels of antioxidant enzymes in arthritic rats were observed. On treatment with the drug, the above changes were reverted back to near normal levels. The increment in CRP level and ESR observed in arthritic animals were found to be significantly restored in SA treated rats. There were no significant changes in sole drug-administered normal rats. Semecarpus anacardium Linn. nut extract significantly decreased the paw edema and arthritic score in arthritic rats on administration, whereas in untreated arthritic rats, there was a significant edema in the hind paw.     

Hypoglycemic and antihyperglycemic effect of Semecarpus anacardium Linn in normal and streptozotocin-induced diabetic rats

The effect of ethanolic extract of dried nuts of Semecarpus anacardium on blood glucose was investigated in both normal (hypoglycemic) and streptozotocin-induced diabetic (antihyperglycemic) rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The ethanolic extract of S. anacardium (100 mg/kg) reduced the blood glucose of normal rats from 85.83 +/- 1.55 to 65.83 +/- 2.20 mg/dl, 3 h after oral administration of the extract (p < 0.05). It also significantly lowered blood glucose levels in streptozotocin-induced diabetic rats from 335.33 +/- 4.90 to 132.17 +/- 4.49 mg/dl, 3 h after oral administration of the extract (p < 0.05). The antihyperglycemic activity of S. anacardium was compared with tolbutamide, a sulfonyl urea derivative used in diabetes mellitus.     

Effect of Semecarpus anacardium Linn. nut extract on mammary and hepatic expression of xenobiotic enzymes in DMBA-induced mammary carcinoma

Breast cancer is the major cause of cancer death in women worldwide. Environmental risk factors particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH) are likely to account for a much higher mortality. Xenobiotic metabolising enzymes in breast tissue are potentially important determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. The well known carcinogen 7,12-dimethylbenz(a)anthrazene of PAH family was given (25 mg/ml) orally by gastric intubation to induce mammary carcinoma in Sprague-Dawley rats. Increased level of cytochromes (P₄₅₀, B₅), EROD, PROD activities, Phase I biotransformation enzymes (NADPH-cytochrome (P₄₅₀) reductase, NADPH-cytochrome (b₅) reductase, epoxide hydrolase) and expression of CYP1A1, CYP1A2 and CYP1B1 in liver and breast tissue microsome were documented in DMBA treated group. Phase II enzyme activities (glutathione-S-transferase, gluthatione peroxidase, gluatathione reductase, UDP-glucuronyl transferease) were decreased markedly in cancerous rats. The nut extract of Semecarpus anacardium was administered orally (200 mg/kg body wt/day) to the mammary carcinoma rats for 14 days. Drug treatment restored back the altered Phase I and II biotransformation enzymes thus achieving complete detoxification of the carcinogen. These findings suggest that S. anacardium can effectively modulate the catabolism of xenobiotics in rats.     

Therapeutic effect of Semecarpus anacardium Linn. nut milk extract on carbohydrate metabolizing and mitochondrial TCA cycle and respiratory chain enzymes in mammary carcinoma rats

Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have evaluated the effect of S. anacardium nut milk extract on carbohydrate metabolizing enzymes and mitochondrial tricarboxylic acid cycle and respiratory enzymes in liver and kidney mitochondria of dimethyl benzanthracene-induced mammary carcinoma in Sprague-Dawley rats. Mammary carcinoma-bearing rats showed a significant rise in glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase) and a simultaneous fall in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase). The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome C oxidase were significantly lowered in mammary carcinoma-bearing rats when compared with control rats. S. anacardium nut extract administration to tumour-induced animals significantly lowered the glycolytic enzyme activities (hexokinase, phosphoglucoisomerase and aldolase) and there was a rise in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase), which indicated an antitumour and anticancer effect. Comparison of normal control rats and rats administered S. anacardium only as drug control animals showed no significant variations in enzyme activities. S. anacardium nut extract administration to dimethyl benzanthracene-tumour-induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.     

Anti-inflammatory and anti-hyperlipidemic effect of Semecarpus anacardium in a High fat diet: STZ-induced Type 2 diabetic rat model

Introduction

Semecarpus anacardium, known as marking nut, has been used in indigenous system of medicine against various ailments.

Aim

To evaluate the antilipidemic and anti-inflammatory effect of S. anacardium Linn. nut milk extract (SA) in Type 2 diabetic rats.

Materials and methods

Diabetes was induced in rats by feeding them with a high fat diet followed by i.p. of 35 mg/kg body weight of streptozotocin. Diabetic rats were treated with the drugs, SA (200 mg/kg body weight) and metformin (500 mg/kg body weight) for 30 days. Antilipidemic effect of the drug was established by studying the lipoprotein alterations and also the alterations in the lipid profile and lipid metabolizing enzymes in the experimental group of rats. The effect of the drug on the expression of PPAR γ was also studied. To determine the anti-inflammatory effect of the drug, the levels of inflammatory cytokines, TNF-α and IL-6 and also C-reactive protein were determined.

Results and discussion

Semecarpus anacardium nut milk extract at a dosage of 200 mg/kg orally significantly (p < 0.05) reduced and normalized the alterations in the lipid metabolism in diabetic rats effectively than metformin. SA treatment significantly (p < 0.05) increased the mRNA expression of PPAR γ, thereby establishing the antilipidemic effect of the drug. The increase in the levels of inflammatory cytokines were significantly (p < 0.05) brought down to near normal levels on treatment with the drug SA.

Conclusion

The present study thereby establishes the antilipidemic and anti-inflammatory effect of the drug. Thus, by decreasing the alterations in the lipid metabolism and inflammatory status, the drug can effectively improve the insulin sensitivity in rats and can serve as an excellent drug in the treatment of Type 2 diabetes mellitus.     

Potency of Semecarpus anacardium Linn. nut milk extract against aflatoxin B(1)-induced hepatocarcinogenesis: reflection on microsomal biotransformation enzymes.

The effect of Semecarpus anacardium Linn. nut milk extract on host detoxification system in aflatoxin B(1) induced hepatocellular carcinoma, which is a vital mechanism in cancer treatment, was studied in male albino rats. Oral administration of nut extract (200 mg kg(-1)body weight per day for 14 days) is found to be highly effective in inducing phase I and phase II biotransformation enzymes. The obtained results have shown an overall decrease of liver microsomal cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, and aniline hydroxylase with a subsequent decrease of phase II enzymes, glutathione-S-transferase and UDP-glucuronyl transferase in cancer-bearing animals. The Semecarpus anacardium nut extract affords anticancer activity by enhancing both phase I and phase II enzymes to near normal levels. We propose that, much of the anticarcinogenic potency of Semecarpus anacardium nut extract on aflatoxin B(1)-induced hepatocarcinogenesis is mediated through the induction of hepatic biotransformation enzymes.     

Effect of Semecarpus anacardium nut extract on ECM and proteases in mammary carcinoma rats

The early stages of invasion are characterized by the extracellular proteolysis and the accumulation of specialized extracellular matrix (ECM) scaffold, that are responsible for the development of vascular bed, endothelial cell proliferation and invasion of tumour cells. The ground substance of provisional matrix consists of collagen, elastin, glycoaminoglycans and proteoglycans that facilitate the interaction of tumour cells with the host environment. In the present work, we have studied the influence of Semecarpus anacardium nut milk extract on localized differentials of ECM component and proteases involved in matrix metabolism of tumour tissue. Mammary carcinoma was induced in Sprague Dawley rats with 7,12, dimethyl benz(a)anthracene and treated with S. anacardium nut milk extract administered orally for 14 days. The altered amount of ECM components in tumour tissues was almost reverted back to normal level in the drug treated animals. The activities of reported proteases and glycohydrolases were also decreased on treatment with S. anacardium nut milk extract indicating decreased turnover of the matrix. Also, the factors associated with the matrix turnover and expression of MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-2 were restored back to near normal values. The stabilization of the ECM with the decreased activity of proteases might inhibit the epithelial-endothelial interaction and tumour cell migration thus, preventing the adjacent invasion and tumour growth and might be regarded as antineoplastic agent which demands further studies.     

Modulating role of Semecarpus anacardium L. nut milk extract on aflatoxin B(1) biotransformation.

As part of a substantial effort to curtail the adverse health effects posed by aflatoxin B(1), studies have been conducted to elucidate the possible mechanism for the anticarcinogenic action of Semecarpus anacardium nut extract against aflatoxin B(1)-induced hepatocellular carcinoma. Rats are monitored for levels of urinary, serum and liver biomarkers, namely, unmetabolised aflatoxin B(1), and its metabolites aflatoxin M(1), and aflatoxin Q(1), over the course of 2 weeks with nut extract therapy following a single-exposure to aflatoxin B(1). Due to the administration of nut extract, the excretion of unmetabolised aflatoxin B(1) was increased in day 1 urine when compared with rats without drug treatment. In serum and liver which were collected on day 16 and the rest of periodical urine samples showed aflatoxin B(1) and its metabolites in undetectable levels. The nut extract administration induced cytochrome P(450), glutathione, and glutathione-S-transferase levels in liver homogenates of aflatoxin B(1)-treated rats. These data seem to indicate that anticarcinogenic action by Semecarpus anacardium nut extract is possibly via suppression of aflatoxin B(1)activation and through interaction with microsomal-activating components. Previous evidence from this laboratory about the potency of Semecarpus anacardium nut extract against aflatoxin B(1)-induced hepatocellular carcinoma together with the present results suggest that extremely effective therapeutic protection can be achieved by this drug against aflatoxin B(1)-mediated ill effects.     

Potential antidiabetic effect of the Semecarpus anacardium in a type 2 diabetic rat model

Semecarpus anacardium Linn. nut milk extract (SA) was evaluated for its antidiabetic role in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding high-fat diet for 2 weeks followed by single intraperitoneal injection of streptozotocin 35 mg/kg body weight. Diabetic rats were treated with SA orally at a dosage of 200 mg/kg body weight daily for 30 days. Metformin (500 mg/kg body weight, orally) was used as a reference drug. SA significantly (p < 0.05) reduced the blood glucose levels and decreased the levels of HbA1c and the glucose intolerance. SA treatment significantly (p < 0.05) decreased the increase in lipid profile. The levels of urea, uric acid and creatinine were restored to near normal levels when compared with control diabetic rats. The histopathological abnormalities were also found to be normalized after treatment with SA nut milk extract. The potential antihyperglycemic action of SA is plausibly due to its underlying antioxidant role.     

Modulation of oxidative/nitrosative stress and mitochondrial protective effect of Semecarpus anacardium in diabetic rats

Objectives Oxidative and nitrosative stress play an important role in the complications of diabetes mellitus. Free radicals are produced when there is an electron leak in the mito‐chondria and a change in the mitochondrial membrane potential. The present study was undertaken to investigate the role of Semecarpus anacardium in protecting the mito‐chondria by modulating the production of reactive oxygen species and reactive nitrogen species in diabetic rats. Methods Diabetes was induced using streptozotocin at a dose of 50 mg/kg body weight and, starting 3 days after the induction, Semecarpus anacardium nut milk extract was administered for 21 days. The same duration of study was used for control, diabetes‐induced and drug control groups, together with a group treated with metformin. After the experimental period, the animals were sacrificed and the levels of superoxide, hydrogen peroxide, nitrate and nitrite were estimated. Changes in mitochondrial membrane potential, intracellular reactive oxygen species and intracellular calcium were also determined. Confocal laser microscopic images were taken for mitochondria isolated from the liver and kidneys. Key findings The results of the study revealed that Semecarpus anacardium was able to decrease the production of reactive oxygen and nitrogen species, and reverse the changes in mitochondrial membrane potential and the influx of calcium into the mitochondria. Conclusions The mitochondrial protective effect may be mediated by scavenging of free radicals and complexing of metal ions by virtue of the antioxidative effect of Semecarpus anacardium.     

Hypoglycemic and antiperglycemic effects of Semecarpus anacardium linn in normal and alloxan-induced diabetic rats

The effect of ethanolic extract of dried nuts of Semecarpus anacardium on blood glucose level was investigated in both normal and alloxan induced diabetic rats. The blood glucose levels were measured at 0, 1, 2 and 3 hours after the treatment. The ethanolic extract of S. anacardium (100 mg/kg) reduced the blood glucose of normal rat from 84 +/- 1.4 to 67 +/- 1.7 mg/dl, 3 hours after oral administration of the extract (P < 0.05). It also significantly lowered blood glucose level in alloxan induced diabetic rat from 325 +/- 2.2 to 144 +/- 1.4 mg/dl, 3 hours after oral administration of the extract (P < 0.05). The antihyperglycemic activity of S. anacardium was compared with tolbutamide, an oral hypoglycemic agent.     

Semi-preparative HPLC preparation and HPTLC quantification of tetrahydroamentoflavone as marker in Semecarpus anacardium and its polyherbal formulations

Application of modern scientific knowledge coupled with sensitive analytical technique is important for the quality evaluation and standardization of polyherbal formulations. Semecarpus anacardium, an important medicinal plant with wide medicinal properties, is frequently used in a large number of traditional herbal preparations. Tetrahydroamentoflavone (THA), a major bioactive biflavonoid was selected as a chemical marker of S. anacardium and RP-semi-preparative HPLC conditions were optimized for the isolation of tetrahydroamentoflavone. HPTLC analytical method was developed for the fingerprinting of S. anacardium flavonoids and quantification of tetrahydroamentoflavone. The method was validated in terms of their linearity, LOD, LOQ, precision and accuracy and compared with RP-HPLC-DAD method. The methods were demonstrated for the chemical fingerprinting of S. anacardium plant parts and some commercial polyherbal formulations and the amount of tetrahydroamentoflavone was quantified. HPTLC analysis showed that S. anacardium seed contained approximately 10 g kg(-1) of tetrahydroamentoflavone. The methods were able to identify and quantify tetrahydroamentoflavone from complex mixtures of phytochemicals and could be extended to the marker-based standardization of polyherbal formulations, containing S. anacardium.     

Anti-inflammatory and anti-osteoarthritis effect of Mollugo pentaphylla extract

Context: Mollugo pentaphylla L. (Molluginaceae) extract (MPE) has been reported to have anti-inflammatory effect on MSU-induced gouty arthritis in a mouse model.

Objective: This study examined the anti-inflammatory activities of an MPE in vitro and anti-osteoarthritis effects on monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in vivo.

Materials and methods: The dried whole plants of M. pentaphylla were extracted with 70% ethanol under reflux. The anti-inflammatory effect of MPE was evaluated in vitro in lipopolysaccharide (LPS)-treated RAW264.7 cells. The anti-osteoarthritic effect of MPE was investigated in a Sprague–Dawley rat model of MIA-induced OA. Each seven male rats were orally administered MPE (75, 150 or 300?mg/kg) or the positive control drug indomethacin (1?mg/kg) 3?days before MIA injection and once daily for 11?days thereafter. After the treatment with MPE, no evidence of systemic adverse effects was observed in any study group.

Results: MPE exhibited anti-inflammatory activity via inhibition of the production of NO (57.8%), PGE2 (97.1%) and IL-6 (93.2%) in LPS-treated RAW264.7 cells at 200?μg/mL. In addition, MPE suppressed IL-1β (60.9%), TNF-α (37.9%) and IL- 6 (40.9%) production and suppressed the synthesis of MMP-2, MMP-9 and COX-2 in the MIA-induced OA rat model.

Conclusions: These results demonstrate that MPE exerts potent anti-inflammatory activities and protects cartilage in an OA rat model. This might be a potential candidate for therapeutic OA treatment.     

Anti-inflammatory effect of Stereospermum suaveolens ethanol extract in rats

The anti-inflammatory effect of the ethanol extract of Stereospermum suaveolens (Roxb.) DC (Bignoniaceae) bark given orally at the dose of 200 and 400?mg/kg body weight was studied in rats using the carrageenan-, dextran-, and histamine-induced hind paw edema, and cotton pellet-induced granuloma formation models. Indomethcin at the dose of 10?mg/kg body weight was used as a standard drug. The extract (400?mg/kg body weight per os) showed maximum inhibition of edema 64.6, 53.48, and 50.06% at the end of 3?h with carrageenan-, dextran-, and histamine-induced rat paw edema, respectively. The extract (400?mg/kg) exhibited significant reduction (34.77%) in granuloma weight in the cotton pellet-induced granuloma model. From these results it could be concluded that, the ethanol extract of Stereospermum suaveolens possesses maximum anti-inflammatory activity in a dose-dependent manner, in various experimental models.     

Anti-inflammatory effect of petroleum ether extract of Vitex negundo leaves in rat models of acute and subacute inflammation

The anti-inflammatory effect of a petroleum ether extract of Vitex negundo Linn (Verbenaceae) leaves, (PEVNL) (250 and 500?mg/kg, p.o.), was evaluated in carrageenan-induced hind paw edema and cotton pellet granuloma models. Diclofenac sodium was used as a standard drug. The biochemical parameters were estimated in serum. In carrageenan-induced rat paw edema model PEVNL exhibited significant (p?<?0.01) inhibition of edema volume at 4?h in a dose-dependent manner. In the cotton pellet granuloma model, dry weight of cotton pellets was significantly inhibited in a dose-dependent manner with maximum effect noticed at 500?mg/kg, p.o. Both doses of PEVNL were found to normalize the increased alkaline phosphatase, acid phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) and reversed the decreased serum albumin. In conclusion, PEVNL exhibited anti-inflammatory activity in acute and subacute models. At a dose of 500?mg/kg, p.o., PEVNL was found to possess maximum activity, and this effect was comparable with reference drug diclofenac sodium (5?mg/kg, p.o.).     

Anti-inflammatory effect of Pinus sibirica oil extract in animal models

The anti-inflammatory effect of the oil extract of seeds of Pinus sibirica Du Tour was evaluated and compared with phenylbutazone. Oral administration of this extract at a dose of 300 mg/kg showed anti-inflammatory activity in the carrageenin-induced edema test in rats. In addition, P. sibirica oil extract showed analgesic properties in the hot-plate test and antipyretic properties in adjuvant-induced local hyperthermia, both in rats. In conclusion, these results provide evidence for the potential usefulness of P. sibirica oil extract, a defined mixture of long-chain polyunsaturated fatty acids, sterols, tocopherols and polyphenols, in inflammatory disorders.     

猪胆干膏的抗炎作用及作用机制的研究

目的 研究猪胆干膏的抗炎作用.方法 采用二甲苯致小鼠耳肿胀,醋酸致小鼠腹腔毛细血管通透性增加,角叉菜胶致大鼠足跖肿胀等模型观察猪胆干膏的抗炎作用,并测定前列腺素E2（PGE2）、一氧化氮（NO）含量及超氧化物歧化酶（SOD）活性.结果 猪胆干膏能显著抑制二甲苯所致小鼠耳肿胀,降低小鼠毛细血管通透性,减轻大鼠足跖肿胀,并降低炎症组织PGE2和NO含量,增强血清SOD活性.结论 猪胆干膏具有明显的抗炎作用,其抗炎机制可能与降低血管通透性、抑制炎症介质生成及增强清除氧自由基、抗脂质过氧化的能力有关.