Anti-Arthritic and Immunomodulatory Potential of Methanolic, n-Hexane, and Ethyl Acetate Fractions of Bark of Acacia modesta on Complete Freund’s Adjuvant-Induced Arthritis in Rats

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Abstract

Rheumatoid arthritis is an autoimmune disorder and topic of interest for researchers due to its increasing frequency and limited treatment. Acacia modesta Wall is known to treat rheumatic disorders in the traditional system of medicinal plants. Traditional medicines are still required for the treatment of this disease due to the large number of side-effects caused by commercial medicines. In the current study, the antiarthritic potential of methanolic extract (AM-metha), n-hexane (AM-hexa) fraction, and ethyl acetate (AM-etha) fraction of the bark of A. modesta against a complete Freund’s adjuvant rat model was evaluated. Evaluation using a digital plethysmometer, macroscopic evaluation, and histopathological evaluation were conducted to determine the paw volume and arthritic scoring. ELISA was performed to assess the PGE2 levels. RT-PCR was used to evaluate the expression levels of MMP2, MMP3, MMP9, NF-κB, IL6, IL1β, TNFα, and VEGF. Biochemical and hematological analyses were also conducted. GC/MS was also carried out to analyze the presence of medicinal compounds. The data revealed a marked reduction in the paw volume, arthritic scoring, and histopathological parameters, indicating the anti-arthritic potential of the plant. Treatment with plant extracts and fractions markedly down-regulated MMP2, MMP3, MMP9, NF-κB, IL6, IL1β, TNFα, and VEGF levels. Similarly, PGE2 levels were also found to be ameliorated in the treatment groups, indicating the immunomodulatory property of plant bark. Plant treatment nearly normalized hematological parameters such as counts of WBCs, RBCs, and platelets, along with Hb content, thereby validating the anti-arthritic activity. GC/MS analysis disclosed the presence of strong anti-inflammatory compounds such as lupeol, oleic acid, and squalene. The study showed that A. modesta possesses anti-arthritic and immunomodulatory potential linked to significant down-regulation of pro-inflammatory and inflammatory biomarkers.

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NF-κB signaling in inflammation

Ting Ting Liu, Lingyun Zhang, Donghyun Joo … (2017)

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.

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Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene.

Mohammad Saleem (2009)

In the Western world, an average of 250 mg per day of triterpenes (member of phytosterol family), largely derived from vegetable oils, cereals, fruits and vegetables is consumed by humans. During the last decade, there has been an unprecedented escalation of interest in triterpenes due to their cholesterol-lowering properties and evidence of this phenomenon include at least 25 clinical studies, 20 patents and at least 10 major commercially triterpene-based products currently being sold all around the world. Lupeol a triterpene (also known as Fagarsterol) found in white cabbage, green pepper, strawberry, olive, mangoes and grapes was reported to possess beneficial effects as a therapeutic and preventive agent for a range of disorders. Last 15 years have seen tremendous efforts by researchers worldwide to develop this wonderful molecule for its clinical use for the treatment of variety of disorders. These studies also provide insight into the mechanism of action of Lupeol and suggest that it is a multi-target agent with immense anti-inflammatory potential targeting key molecular pathways which involve nuclear factor kappa B (NFkappaB), cFLIP, Fas, Kras, phosphatidylinositol-3-kinase (PI3K)/Akt and Wnt/beta-catenin in a variety of cells. It is noteworthy that Lupeol at its effective therapeutic doses exhibit no toxicity to normal cells and tissues. This mini review provides detailed account of preclinical studies conducted to determine the utility of Lupeol as a therapeutic and chemopreventive agent for the treatment of inflammation and cancer.

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Gut Microbiota, Short-Chain Fatty Acids, and Herbal Medicines

Wuwen Feng, Hui Ao, Cheng Peng (2018)

As an important source for traditional medical systems such as Ayurvedic medicine and traditional Chinese medicine, herbal medicines have received widespread attentions from all over the world, especially in developing countries. Over the past decade, studies on gut microbiota have generated rich information for understanding how gut microbiota shape the functioning of our body system. In view of the importance of gut microbiota, the researchers engaged in studying herbal medicines have paid more and more attention to gut microbiota and gut microbiota metabolites. Among a variety of gut microbiota metabolites, short-chain fatty acids (SCFAs) have received most attention because of their important role in maintaining the hemostasis of hosts and recovery of diseases. Herbal medicines, as an important resource provider for production of SCFAs, have been demonstrated to be able to modulate gut microbiota composition and regulate SCFAs production. In this mini-review, we summarize current knowledge about SCFAs origination, the role of SCFAs in health and disease, the influence of herbal medicine on SCFAs production and the corresponding mechanisms. At the end of this review, the strategies and suggestions for further research of SCFAs and herbal medicines are also discussed.