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Structural elucidation and in vivo anti-arthritic activity of β-amyrin and polpunonic acid isolated from the root bark of Ziziphus abyssinica HochstEx. A Rich (Rhamnaceae).

ABSTRACT: Two natural products, compounds 1 and 2 were isolated from the root bark of Ziziphus abyssinica for the first time and were structurally elucidated as β-amyrin and polpunonic acid, respectively. Both compounds were further subjected to an in vivo study in rats to evaluate their anti-arthritic potency. Compared to the arthritic control group, rats treated with different doses of 1 or 2 (3, 10, and 30 mg/kg) exhibited significantly higher total change in body weight as well as lower arthritic scores and total change in paw edema and erythema. Histopathological examinations of the hind paws of the rats further demonstrated the beneficial effects of both compounds as they significantly reversed cartilage erosion, subchondral cyst, and Weichselbaum's lacunae formation. Evidence of bone remodeling was also observed in all groups of rats treated with 1 or 2. Hematological and serum biochemical parameters were not significantly affected by treatment of 1 or 2. Taken together, the results from the present study suggest potential therapeutic benefit of β-amyrin and polpunonic acid in rheumatoid arthritis and related inflammatory disorders.

SUBMITTER: Henneh IT

PROVIDER: S-EPMC11294980 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Structural elucidation and in vivo anti-arthritic activity of β-amyrin and polpunonic acid isolated from the root bark of Ziziphus abyssinica HochstEx. A Rich (Rhamnaceae).

Henneh Isaac T IT Huang Boshi B Musayev Faik N FN Hashimi Rana Al RA Safo Martin K MK Armah Francis A FA Ameyaw Elvis O EO Adokoh Christian K CK Ekor Martins M Zhang Yan Y

Bioorganic chemistry 20200309

Two natural products, compounds 1 and 2 were isolated from the root bark of Ziziphus abyssinica for the first time and were structurally elucidated as β-amyrin and polpunonic acid, respectively. Both compounds were further subjected to an in vivo study in rats to evaluate their anti-arthritic potency. Compared to the arthritic control group, rats treated with different doses of 1 or 2 (3, 10, and 30 mg/kg) exhibited significantly higher total change in body weight as well as lower arthritic scor ...[more]

PMID: 32179280

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Project description:BackgroundThe root bark of Zizyphus nummularia (Rhamnaceae) is traditionally used as an anti-inflammatory agent. The current study aimed to explore the anti-inflammatory activity (in vivo) of a crude ethanolic extract (EE) and the pure identified octadecahydro-picene-2,3,14,15-tetranone (IC) in the root bark of Z. nummularia. IC was further subjected to suitable in vitro and in silico studies to find out the mechanistic pharmacology.MethodsEE (100 and 200 mg/kg, p.o.) and (IC) (400 and 600 μg/kg, p.o.) were subjected to in vivo anti-inflammatory assays to evaluate the anti-inflammatory activity and predict the probable mechanism(s) of action. Suitable acute (carrageenan-induced paw edema, arachidonic acid-induced ear edema, xylene-induced ear edema) and chronic (cotton pellet granuloma) models were employed to investigate in vivo the anti-inflammatory activity. Based on in vivo observation, IC was further subjected to in vitro assays to estimate the inhibition of nitric oxide (NO), prostaglandin-E2 (PGE-2) and tumor necrosis factor-α (TNF-α) production in PBS stimulated RAW 264.7 cells. Based on the observation of in vitro studies, finally, ADME prediction and molecular docking studies of IC were performed for better understanding of interaction of IC with TNF-α.ResultsOral administration of EE (100 and 200 mg/kg) exhibited significant inhibition of carrageenan (p < 0.05) and arachidonic acid (p < 0.05) induced oedema, and the reduced the granuloma tissue formation (p < 0.05) in experimental mice. IC (400 and 600 μg/kg, p.o.) exhibited significant (p < 0.01) inhibition of carrageenan, xylene and arachidonic acid-induced edema, and reduced the granuloma tissue formation. In in vitro assays, IC caused a concentration-dependent inhibition of LPS stimulated NO (up to ~ 67.4% at 50 μM) and TNF-α (~84.5% at 50 μM) production. However, the PGE-2 inhibition did not follow dose dependent pattern. Based on in vitro observations, the molecular docking has been performed on the basis of interaction with TNF-α. In in silico studies, it was observed that IC showed hydrogen bonding with GLN 47 amino acid residue of TNF-α protein.ConclusionsIC possibly produces anti-inflammatory activity through inhibition of TNF-α and NO production.

Dataset Information

Structural elucidation and in vivo anti-arthritic activity of β-amyrin and polpunonic acid isolated from the root bark of Ziziphus abyssinica HochstEx. A Rich (Rhamnaceae).

Publications

Structural elucidation and in vivo anti-arthritic activity of β-amyrin and polpunonic acid isolated from the root bark of Ziziphus abyssinica HochstEx. A Rich (Rhamnaceae).

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