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Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats.

ABSTRACT: The polyherbal formulation containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol ex. Maton has been used for hypertension treatment empirically. Our previous study showed its blood pressure-lowering effect on a rat model of hypertension. However, toxicity data were not available for this polyherbal formulation. This study is aimed at evaluating the acute and subchronic oral toxicity of the polyherbal formulation in rats. The acute toxicity study was conducted on 6 female Wistar rats using the fixed-dose method for the treatment group and 5 female Wistar rats for the control. The single dose of 2,000?mg/kg of the polyherbal formulation was given orally. There were no significant toxic effects and no death observed until the end of the study, and it was showed that the lethal dose 50% (LD50) of the polyherbal formulation was estimated to be more than 2,000?mg/kg. The macroscopic and microscopic examination of vital organs showed no symptoms of toxicity. At the subchronic toxicity study, the polyherbal formulation with 3 dose variations of 252?mg/kg, 1,008?mg/kg, and 4,032?mg/kg was administered for 91 days orally. The lowest dose of 252?mg/kg is equivalent to the daily recommended dose for a human. There were no significant toxic effects observed at all doses on physical sign and symptoms, weight gain, food intake, hematological parameters, biochemical parameters, and macroscopic and microscopic examination of organs. These findings showed that the short- and long-term oral administration of the polyherbal formulation is safe to use within its dose recommendation.

SUBMITTER: Sholikhah EN

PROVIDER: S-EPMC7136774 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats.

Sholikhah E N EN Mustofa M M Nugrahaningsih D A A DAA Yuliani F S FS Purwono S S Sugiyono S S Widyarini S S Ngatidjan N N Jumina J J Santosa D D Koketsu M M

BioMed research international 20200324

The polyherbal formulation containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol ex. Maton has been used for hypertension treatment empirically. Our previous study showed its blood pressure-lowering effect on a rat model of hypertension. However, toxicity data were not available for this polyherbal formulation. This study is aimed at evaluating the acute and subchronic oral toxicity of the polyherbal for ...[more]

PMID: 32309440

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Project description:BackgroundPlants belonging to the genus Terminalia such as Terminalia bellirica and Terminalia sericea are used traditionally to treat several diseases and health disorders. Up to this date, the roots of Terminalia sericea and the fruits of Terminalia bellirica are the mostly studied plant parts. The phytochemical composition and the biological activities of the leaves of both species are not well identified so far.MethodsThe secondary metabolites of Terminalia bellirica and Terminalia sericea leaves were identified using HPLC-PDA-MS/MS. The antioxidant activities of the leaves extracts were determined by DPPH and FRAP assays. The hepatoprotective potential was evaluated in rats with D-galactosamine induced liver damage. The effect of the extracts on the expression of the anti-apoptotic marker Bcl-2 was measured in an immunohistochemical study. The most abundant compounds identified in the studied extracts were docked into Bcl-2: Bim (BH3) interaction surface using molecular operating environment software.ResultsA total of 85 secondary metabolites were identified in the leaf extracts of both species. Ellagitannins such as corilagin, chebulagic acid, galloylpunicalagin, and digalloyl-hexahydroxydiphenoyl-hexoside were found to be the major components in Terminalia bellirica whereas flavonoid glycosides including quercetin rutinoside and quercetin galloyl-glucoside were highly abundant in Terminalia sericea. The studied extracts exhibited pronounced antioxidant activities, moderate anti-apoptotic and hepatoprotective potential. In silico docking experiments revealed that the compounds abundant in the extracts were able to bind to Bcl-2: Bim (BH3) interaction surface with an appreciable binding free energy.DiscussionThe antioxidant and hepatoprotective activities exhibited by the studied extracts might be attributed to the high content of the polyphenols. The anti-apoptotic activity could be due to the interference with the apoptotic pathway mediated by Bcl-2: Bim interaction. These findings support the medicinal relevance of Terminalia bellirica and Terminalia sericea and provide a rational base for their utilization in folk medicine.

Project description:A polyherbal drug composed of leaves of Murraya koenigii L. Spreng, cloves of Allium sativum L., fruits of Garcinia quaesita Pierre, and seeds of Piper nigrum L. is a popular drug which has been used by indigenous practitioners in Sri Lanka for the treatment of diabetes mellitus and dyslipidemia. The acute toxicity assessment was conducted, following a single oral dose of 0.25-2.0?g/kg in healthy rats, and rats were observed up to 14 days. The hot water extract (1.0?g/kg) and the water?:?acetone extract (0.5, 1.0, and 1.5?g/kg) were administered to Wistar rats for 28 days in the subchronic study. Hypoglycemic and antihyperglycemic activities (dose response studies) of cold water, hot water, and water?:?acetone extracts of the polyherbal mixture were evaluated at the doses of 0.5, 1.0, and 1.5?g/kg in healthy and streptozotocin-induced diabetic rats (70?mg/kg, ip), respectively. Acute toxicity study showed that the polyherbal drug did not cause any change in animals throughout the experimental period of 14 days. The administration of the hot water extract and the water?:?acetone extract of the polyherbal drug for 28 days did not produce changes in the selected biochemical and hematological parameters in Wistar rats (p?>?0.05). The histological assessment corroborated the biochemical findings with no significant treatment-related changes in the kidney and liver. The treatment of polyherbal drug significantly lowered the serum glucose concentration compared to the diabetic control rats (p?<?0.05) while it did not lead to a severe reduction of glucose concentration in healthy rats. The hot water and water?:?acetone extracts of the polyherbal drug showed a statistically significant improvement on total area under the glucose tolerance curve in diabetic rats (p?<?0.05), reflecting dose-dependent antihyperglycemic effects of the drug. Based on the results, we conclude that the aforementioned antidiabetic polyherbal remedy is free of toxic/adverse effects at the equivalent human therapeutic dose in healthy Wistar rats and would be a safe therapeutic agent for long-term treatments.

Project description:BackgroundAmomum compactum is one of the basic species of the traditional herbal medicine amomi fructus rotundus, with great pharmacology effect. The system position of A. compactum is not clear yet, and the introduction of this plant has been hindered by many plant diseases. However, the correlational molecular studies are relatively scarce.MethodsThe total chloroplast (cp) DNA was extracted according to previous studies, and then sequenced by 454 GS FLX Titanium platform. Sequence assembly was complished by Newbler. Genome annotation was preformed by CPGAVAS and tRNA-SCAN. Then, general characteristics of the A. compactum cp genome and genome comparsion with three Zingiberaceae species was analyzed by corresponding softwares. Additionally, phylogenetical trees were reconstructed, based on the shared protein-coding gene sequences among 15 plant taxa by maximum parsimony (MP) and maximum likelihood (ML) methods.ResultsThe A. compactum cp genome with a classic quadripartite structure, consisting of a pair of reverse complement repeat regions (IRa/IRb) of 29,824 bp, a large single copy (LSC, 88,535 bp) region as well as a small single copy (SSC, 15,370 bp) region, is 163,553 bp in total size. The total GC content of this cp genome is 36.0%. The A. compactum cp genome owns 135 functional genes, that 113 genes are unique, containing eighty protein-coding genes, twenty-nine tRNA (transfer RNA) genes and four rRNA (ribosomal RNA) genes. Codon usage of the A. compactum cp genome is biased toward codons ending with A/T. Total 58 SSR loci and 24 large repeats are detected in the A. compactum cp genome. Relative to three other Zingiberaceae cp genomes, the A. compactum cp genome exhibits an obvious expansion in the IR regions. In A. compactum cp genome, the ycf1 pseudogene is 2969 bp away from the IRa/SSC border, whereas in other Zingiberaceae species, it is only 4-5 bp away from the IRa/SSC border. Comparative cp genome sequences analysis of A. compactum with other Zingiberaceae reveals that the gene order and gene content differ slightly among Zingiberaceae species. The phylogenetic analysis based on 67 protein-coding gene sequences supports the phylogenetic position of A. compactum.ConclusionsThe study has identified unique features of the A. compactum cp genome which would be helpful for us to understand the cp genome evolution and offer useful information for phylogenetics and further studies of this traditional medicinal plant.

Project description:BackgroundOxidative stress and endothelial cell dysfunction induced by high-altitude hypoxia have important roles in the pathological process of high-altitude pulmonary hypertension (HAPH). Tannins present in Terminalia bellirica (Gaertn.) Roxb. (TTR) have pharmacological activities that produce oxidation resistance and exert anti-inflammatory effects. Whether TTR exerts a protective effect on HAPH remains unknown.MethodsA rat model of HAPH was established. The mean pulmonary arterial pressure (mPAP) of the animals was measured, the serum levels of SOD, MDA, and GSH-Px were measured using ELISA, and the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in the lung tissue of each group of rats was measured using Western blotting. Pathological changes in the lung tissue were also observed. A model of damage to H2O2-induced pulmonary artery endothelial cells (PAECs) was generated, and cell proliferation was measured using CCK-8 assays. Flow cytometry was used to measure ROS levels in PAECs. Western blotting was used to detect the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in PAECs.ResultsThe hemodynamic and pathologic findings showed that the mPAP of HAPH rats increased markedly, and the vascular wall thickness increased (P < 0.05). TTR reduced mPAP, alleviated or slowed pulmonary arterial remodeling, increased GSH-Px and SOD activity, lowered the level of MDA (P < 0.05), and downregulated the expression of Bax in the lung tissues of HAPH rats, while the expression of Bcl-2, Nrf2, and HO-1 was upregulated (P < 0.05). The results of the cell experiments showed that TTR inhibited H2O2-induced PAEC apoptosis and ROS production (P < 0.05), downregulated the expression of Bax in PAECs, and upregulated the expression of Bcl-2, Nrf2, and HO-1 (P < 0.05).ConclusionThe results suggest that TTR reduces pulmonary arterial pressure, decreases oxidative stress during HAPH, and exerts protective effects in rats with HAPH and that its mechanism of action is related to regulation of the Nrf2/HO-1 signaling pathway.

Dataset Information

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats.

Publications

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing <i>Allium sativum</i> L., <i>Terminalia bellirica</i> (Gaertn.) Roxb., <i>Curcuma aeruginosa</i> Roxb., and <i>Amomum compactum</i> Sol. ex. Maton in Rats.

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