Protective effects of Rubus tereticaulis leaves ethanol extract on rats with ulcerative colitis and bio-guided isolation of its active compounds: A combined in silico, in vitro and in vivo study

Ulcerative colitis (UC) is a persistent type of inflammatory bowel disease (IBD) that affects the colon mucosa. UC is largely associated with oxidative stress and inflammation that cause damage to colon tissue [1].

Oxidative stress and inflammation form the basis of the pathogenesis of many diseases. Free radicals produced by the physical and biochemical processes that occur in the human body damage various biomolecules that are important for the body, thereby causing various diseases [2]. Inflammation is an indeterminate physiological response of the body to damage caused by endogenous or exogenous agents, and is an inevitable limited response of the body to spontaneous exposure when the tissue is exposed to chemical, mechanical or biological damage. Therefore, inflammation acts as one of the defense barriers of the organism. Keeping inflammation under control plays an important role in the treatment of chronic inflammation-related diseases such as arthritis, osteoarthritis, sclerosis, arteriosclerosis, Alzheimer's, diabetes, insulin-resistance, obesity, allergies, asthma, chronic bronchitis, cancer, tuberculosis, retinitis, psoriasis, lung fibrosis, and chronic gastritis [3].

Reactive oxygen species (ROS) are signaling molecules that play an important role in the progression of inflammatory diseases [4]. Antioxidants reduce health risks associated with oxidative stress caused by intense ROS such as free radicals. It has been found that certain polyphenol-based diets, including polyphenols that are potent antioxidant and anti-inflammatory agents, have therapeutic efficacy in reducing inflammation and oxidative stress [5]. Furthermore, phenolic compounds and flavonoids present in plants are known to have antioxidant, anti-cancer, antimicrobial, antiviral and anti-inflammatory activities [6]. As a result, it is crucially important to conduct research on medicinal plants and their polyphenolic-rich extracts.

Although aminosalicylic acid, corticosteroids, and thiopurines used for the prevention and treatment of IBD today have somewhat improved the quality of life of patients with IBD, they have not been effective at all stages of the disease [7]. Therefore, new drugs with less side effects than those currently used are needed.

The genus Rubus, a member of the Rosaceae family, is represented by naturally grown 10 taxa in Turkey [8]. Rubus species including Rubus tereticaulis in various regions of Turkey in traditional medicine are generally used to treat wounds, cuts and burns as well as skin diseases like eczema and psoriasis [9]. In addition, different parts of the Rubus species (fruit, leaves, and roots) are used in the treatment of kidney and prostate inflammation, hemorrhoid, diarrhea, inflammatory small bowel diseases, diabetes mellitus, rheumatism, sore throat, colds, influenza, and cardiovascular diseases, also as an immune system booster and hemostatic [10,11]. In particular, it was noted in the literature that the leaves of Rubus tereticaulis are used by the public for anti-inflammatory purposes [12].

Scientific studies on Rubus species have revealed that these species harbor antimicrobial, radical scavenging, anticonvulsant, muscle relaxant, anti-inflammatory and antinociceptive activities [11]. Phytochemical analyses of Rubus species have indicated the presence of flavonoids (quercetin, kaempferol, etc.) and phenolic acids (caffeic acid, chlorogenic acid, etc.). Additionally, the presence of catechins, pectins, carboxylic acids, anthocyanins, vitamin C, and saturated or unsaturated fatty acids has also been demonstrated by earlier reports [13,14]. To the best of our knowledge, there is no scientific information regarding the chemical composition and biological activity of Rubus tereticaulis leaves. Therefore, the aim of this study was to investigate the protective effects of Rubus tereticaulis leaves ethanol extract (RTME) on acetic acid-induced colitis in rats and obtain the active compounds from RTME through in vitro anti-inflammatory and antioxidant activity by bioassay-directed isolation.

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