Evaluation of Hepatoprotective Potential of Polyherbal Preparations in CCl4-Induced Hepatotoxicity in Mice.

Background: Polyherbal formulations (PLFs) have been widely used for liver protection, treatment for hepatic dysfunction, and regeneration. They can also enhance appetite and protect the gastrointestinal tract from injury. In spite of the prevalent use, there is a need of scientific evidence on their effectiveness and safety. The objective of the present study was to assess the hepatoprotective effect of polyherbal formulations (commercially available in Bangladesh namely Heptaliv, Holyliv, Icturn, and J-deenar) in CCl4-induced hepatotoxicity in mice. Methods: In this study, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, per os.) followed by single subcutaneous injection of CCl4 (1 ml/kg body weight, diluted with olive oil in 1 : 1 ratio) on day 8. Twenty-four hours after CCl4 administration, the mice were monitored for the effects of PLFs on liver morphology, biochemical parameters including serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin. Phenobarbitone-induced sleeping time and histopathology changes in liver tissues were also monitored. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in AST, ALT, ALP, and total bilirubin. Phenobarbitone-induced sleeping time and infiltration of inflammatory cells and centrizonal necrosis on histological examination of liver demonstrated hepatic injury after CCl4 administration. However, the administration of Icturn and J-deenar polyherbal formulations at the higher dose significantly decreased the levels of AST, ALT, ALP, and total bilirubin. Moreover, pentobarbitone-induced sleeping time and histopathological analysis also revealed significant improvement as result of treatment with formulations Icturn and J-deenar. Conclusion: Our results confirmed that polyherbal formulations (Icturn and J-deenar) can significantly prevent CCl4-induced hepatotoxicity in mice, demonstrating their protective effect for liver.

Disposal Practices of Unused and Leftover Medicines in the Households of Dhaka Metropolis.

Background: This fact-finding study aimed to attain an overall idea and knowledge about medicine disposal practices in Dhaka Metropolitan households. Methods: This mixed study (both quantitative and qualitative) was orchestrated to inspect the household leftover medicine disposal pattern's governing status. A cross-sectional survey was conducted following a structured questionnaire and key informant interview with a household person and in-depth interviews with the top pharmaceutical and government officials. Results: Findings disclose that, for most of the key informants, the terms "drug disposal" and "drug pollution" were unknown; more precisely, 67% and 74% of key informants even did not hear these two terms. Almost all (87%) households faced undesired incidents due to the insecure storage of medicines. People disposed of excess and expired medication in regular dustbins (47%), threw out of the window (19%), flushed within commode (4%), burnt in fire (2%), and reused (4%). A good percentage of people (21%) returned unexpired drugs to the pharmacy and bought other medicines on a need basis. A total of 72% wanted a medicine take-back program, and 100% agreed on mass education on this issue. Officials of pharmaceuticals conferred mixed opinion: top-ranked pharmaceuticals will adopt leftover medicine disposal practices; middle and low-ranked pharmaceutical companies are reluctant, merely denied mentioning the less important issue. Conclusions: The absence of mass awareness and standard laws and policies may explain these existing aberrant practices.

Complement activation in obesity, insulin resistance, and type 2 diabetes mellitus.

Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity, insulin resistance, diabetes, dyslipidemia, and atherosclerosis. The complement system was originally viewed as a supportive first line of defense against microbial invaders, and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes, involving in such diverse processes as clearance of the immune complexes, complementing T and B cell immune functions, tissue regeneration, and metabolism. The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity, insulin resistance and diabetes mellitus. In addition, we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy, nephropathy and neuropathy, highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.

Ethnopharmacological Inspections of Organic Extract of Oroxylum indicum in Rat Models: A Promising Natural Gift.

The stem bark of Oroxylum indicum (O. indicum) was aimed at testing for anti-inflammatory, antiulcerative, antihyperglycemic, and antidyslipidemic activities. Liver enzyme concentration (SGPT, SGOT) had also been assessed. After being extracted in organic solvent, 3 distinct doses, 100, 200, and 400 mg/kg b.w. (p.o.), were used. For edema formation 0.1 ml carrageenan at a dose of 1% w/v was injected into paw of left hind. It showed a fall of edemas 37.50%, 48.34%, and 55.83% while used doses were 100, 200, and 400 mg/kg b.w. (p.o.) individually. The EtOH extract of O. indicum (50%) and its fractions PET, CLF, EtOAc, and nBUT were studied against ethanol-induced gastric mucosal damage. Only PET and n-BuOH exhibited the highest percentage of protection and were 96% and 99%, respectively, persuaded by ethanol. In OGTT glibenclamide revealed reduction of glucose level to 7.55 ± 0.22 mmol/L from 10.57 ± 0.32 mmol/L after 30 minutes. Antihyperglycemic activities were assessed for 8- and 12-week duration in diabetic rats. Glibenclamide reduced glucose level from 33.50±0.31 to 7.90±0.19 mmol/L in 12 weeks. In 12 and 8 weeks, combination therapy lowered blood glucose level to a normal extent by 79% and 61% individually. In antidyslipidemic activities after 12-week treatment, it revealed simvastatin; MEOI (400 mg/kg b.w.) and combination of both reduced TC level by 44%, 28%, and 48% consequently followed by TG and LDL. In 8-week treatment, HDL levels were increased by 34%, 13%, and 36%, and in 12 weeks increased by 36%, 8%, and 38% consequently. Liver enzyme concentration after 12 weeks of treatment with glibenclamide, 400 mg/kg b.w. (p.o.) of MEOI and combination of both, exhibited the fact that concentration of SGPT showed downturn by 43.23%, 8.01%, and 54.86% and SGOT by 42.40%, 5.31%, and 44.85%. This study remarked that O. indicum has anti-inflammatory, antiulcer, antidiabetic, and antidyslipidemic potentials but has no ameliorative effect on liver enzyme.

Wound healing effect of Euphorbia hirta linn. (Euphorbiaceae) in alloxan induced diabetic rats.

BACKGROUND: Euphorbia hirta linn., is a species of Euphorbiaceae family. They are known as asthma plant, barokhervi. The plant E. hirta is famous for its medicinal importance among the tribal population. It is a common practice to use the whole to heal wounds. Several pharmacological properties including antiseptic, anti-inflammatory, antidibetic, antispasmodic, antibacterial, antiviral, antifungal, anticonvulsant, nootropic, antifertility and aphrodisiac properties have already been reported for this plant. The aim of present work was to evaluate the wound healing property in diabetic animals by oral and topical administration of ethanolic extract of E. hirta whole plant. METHODS: The ethanolic extract of E. hirta was subjected to determine the total phenolic content and total flavonoid content using galic acid and quercetin, respectively as standard. A single injection of alloxan monohydrate (120 mg/kg, i.p.) prepared in normal saline was administered to produce diabetes in rats, after overnight fasting. For analyzing the rate of contraction of wound, excision wounds sized 4.90cm2 and of 2 mm depth were used. Oral (100, 200 and 400 mg/kg/day; p.o.) and topical treatment with the extract (5% and 10% ointment 50 mg/kg/day) and standard (5% povidone iodine ointment 50 mg/kg/day) was started on the day of induction of wound and continued up to 16 days. The means of wound area measurement between groups at different time intervals were compared using ANOVA and Dunnet's test. The diabetic wound healing mechanism was studied by measuring the plasma level of glucose, malondialdehyde (MDA) and nitric oxide (NO) in both control and treated groups. For the confirmation of activity, histopathology of the wounds tissues from excision wound model was performed. RESULTS: Phytochemical investigations showed the presence of various phytoconstituents (carbohydrates, saponins, alkaloids, glycosides, steroids, flavonoids, tannins). In the ethanolic extract of E. hirta the total phenol content was 285 ± 3.22 mg/g whereas the total flavonoid content was 118.46 ± 1.85 mg/g. In the present study, E. hirta caused significant wound closer both orally (35.92%, 44.69% and 61.42% at the doses of 100, 200 and 400, respectively) and topically (32.86% and 36.32% at the doses of 5% and 10%) treated groups as compared to diabetic control. However, the orally treated groups showed more significant effect than the topically treated groups. Moreover, oral administration of E. hirta ethanolic extract significantly reduced the blood glucose levels in diabetic wound rats (p < 0.01) on day 8 and day 16 as compared to the diabetic wound control (p < 0.01). On the other hand, topical application of E. hirta did not influence the blood glucose levels in diabetic rats (p > 0.05). It also demonstrated a significant decrease in the plasma levels of lipid malondialdehyde and nitric oxide. The results of biochemical parameters were further supported by the histopathological changes of different organs (liver, pancrease, kidney, heart and skin from wound area) which were evidenced through a decrease in inflammatory cell infiltration. CONCLUSION: The present study demonstrates that E. hirta whole plant extract promotes healing of wounds more significantly as compared to diabetic control rats, where healing is otherwise delayed.

Inhibition of proinflammatory mediators by coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea, on inflammation-induced animal model.

ETHNOPHARMACOLOGICAL RELEVANCE: Careya arborea Roxb. (Lecythidaceae) is a large tree found throughout India in deciduous forests and grasslands. C. arborea is traditionally used in tumors, inflammation, anthelmintic, bronchitis, epileptic fits, astringents, antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, tooth ache, and ear pain. AIM OF THE STUDY: In our previous work, the methanolic extract of Careya arborea stem bark showed significant anti-inflammatory activity. As a continuity of that work, this study aimed at the isolation and evaluation of the anti-inflammatory effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark. Further, to give an insight into the underlying mechanism of action of the compound on the modulation of proinflammatory mediators. MATERIALS AND METHODS: Methanolic extract of Careya arborea stem bark was suspended in water, and sequentially fractionated with n-hexane and ethyl acetate. Further ethyl acetate fraction was subjected to medium pressure liquid chromatography (MPLC) to isolate the active molecules. The isolated compounds were characterized by the various spectral techniques namely UV, IR, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HMBC and Mass spectral techniques. In vitro COX-1 and COX-2 enzyme inhibition assays using human whole blood was performed to investigate the inhibitory effect of the isolated compounds. The resulted potent COX-2 inhibitor of the isolated constituents compound 5, designated as coumaroyl lupendioic acid (CLA), was investigated in carrageenan induced inflammation and its effect was also compared with betulinic acid (BA) at the doses of 10 and 20mgkg-1, p.o. using indomethacin and celecoxib (10 and 20mgkg-1, p.o., respectively) as reference drugs. The effect of CLA on the production of NO, MPO, PGE2, TNF-α, IL-1ß and IL-6 were assessed. In addition, the histopathology and immunohistochemistry (NF-Ò¡B, COX-2 and TNF-α protein expression) in paw tissues were also carried out. RESULTS: The chromatographic fractionation of the methanolic extract resulted in isolation of six new derivatives of lupane type triterpenes for the first time from the stem bark of C. arborea; 3ß-hydroxy-lup-5,20 (29),21-trien-28-oic acid (Compound 1), 1, 3, 13, 16-tetrahydroxy-lup-9(11), 20(29)-diene-28-oic acid (Compound 2), 1, 7-di hydroxy betulinic acid (Compound 3), 3ß-O-dihydrocinnamyl betulinic acid (Compound 4), 3ß-O-trans-coumaryl-lup-6, 9(11), 20(29)-triene-27, 28-dioic acid (Compound 5), 16ß-hydroxy-2, 3-seco-lup-5, 20(29)-dien-2, 3, 28-trioic acid (Compound 6). Among the all isolated compounds 3ß-O-trans-coumaryl-lup-6, 9(11), 20(29)-triene-27, 28-olioic acid designated as coumaroyl lupendioic acid (CLA) showed higher COX-2 selectivity which is comparable to reference drug (celecoxib). CLA significantly reduced carrageenan induced inflammation whereas CLA revealed greater effect as compared to BA at the similar corresponding doses. Moreover, CLA significantly inhibited pro-inflammatory mediators elevated by carrageenan. CLA also preserved the tissue architecture as evidenced by the histopathology. Furthermore, immunohistochemical studies revealed that CLA significantly down regulated NF-Ò¡B, COX-2 and TNF-α protein expression. CONCLUSION: The study gives an insight into the molecular mechanisms of coumaroyl lupendioic acid and suggests that the down-regulations of proinflammatory mediators provide credence to the ethno botanical use of the plant in the management of inflammation.

Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats.

BACKGROUND: The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. METHODS: The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. RESULTS: P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract's doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema. CONCLUSIONS: The investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.

Inhibitory effect of Careya arborea on inflammatory biomarkers in carrageenan-induced inflammation.

CONTEXT: Careya arborea Roxb. (Lecythidaceae) has multiple applications in traditional medicine; it exhibits analgesic, antibacterial, anti-inflammatory, antiulcer, and protective effects. However, the effect of C. arborea on biochemical and immmunological inflammatory mediators has not been explored. OBJECTIVE: The present study investigates the anti-inflammatory potential of the methanol extract of C. arborea stem bark and further assesses its possible mechanism on the modulation of inflammatory biomarkers. MATERIALS AND METHODS: Anti-inflammatory activity of C. arborea methanol extract (CAME) was evaluated (100 and 200 mg/kg, p.o) using indomethacin (10 mg/kg, p.o) as the standard drug in Wistar albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. The anti-inflammatory mechanism was studied by measuring malondialdehyde (MDA), C-reactive protein (CRP), nitric oxide (NO), myeloperoxidase (MPO), TNF-α, and IL-1ß levels in both control and treated groups. A protocol has also been established to quantify quercetin and betulinic acid content in CAME using HPTLC fingerprint. RESULTS: Careya arborea significantly (p < 0.001) decreased carrageenan-induced paw edema, showed a reduction of 48.87 and 65.53% at doses of 100 and 200 mg/kg, respectively. Moreover, CAME significantly decreased the MDA, CRP, NO, and MPO levels, elevated by carrageenan induced inflammation. CAME also markedly down-regulated serum TNF-α and IL-1ß levels. These findings were further supported by the histological study. The content of quercetin and betulinic acid in CAME was found to be 0.177 and 3.14%, respectively. CONCLUSION: Several mechanisms, including the inhibition of pro-inflammatory cytokines, enzymes and mediators release, appear to account for the anti-inflammatory potential of C. arborea.