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Abstract: For decades Experimental Autoimmune Encephalitis (EAE) has remained as an unsurpassed multiple sclerosis (MS) animal model. C-Phycocyanin (C-Pc) has been reported to exhibit pharmacological properties that may be expected to symptomatically improve EAE and MS. However, in this paper we reveal a basic underlying mechanism that may provide a new approach to the rationale of the overall beneficial effect of this natural antioxidant. We demonstrate that C-Pc is able to trigger mechanisms preventing or downgrading EAE expression and induces a regulatory T cell (Treg) response, in peripheral blood mononuclear cells (PBMC) from MS patients. These results agree with reports suggesting that Treg limit acute MS attacks and that C-Pc may act as a neuroprotector and thereby reverts the organic and functional damage in neurodegenerative disorders of the central nervous system (CNS). Moreover, evidence is provided on the antioxidant activity of C-Pc within the CNS, intended to improve the myelin and axonal damage of EAE induced Lewis rats. Our results indicate that specific Treg activation may represent a central and essential mechanism in supporting the therapeutic potential of C-Pc for MS and may lead to new and more effective therapies; this property would then complement and enhance other proven active principles such as interferons (IFN), giving rise to combined therapies. [ABSTRACT FROM AUTHOR]

The fruit of Tetradium ruticarpum (FTR) known as Tetradii fructus or Evodiae fructus (Wu-Zhu-Yu in Chinese) is a versatile herbal medicine which has been prescribed in Chinese herbal formulas and recognized in Japanese Kampo. FTR has been clinically used to treat various diseases such as headache, vomit, diarrhea, abdominal pain, dysmenorrhea and pelvic inflammation for thousands of years. The present paper aimed to provide comprehensive information on the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, drug interaction and toxicology of FTR in order to build up a foundation on the mechanism of ethnopharmacological uses as well as to explore the trends and perspectives for further studies. This review collected the literatures published prior to July 2020 on the phytochemistry, pharmacology, pharmacokinetics and toxicity of FTR. All relevant information on FTR was gathered from worldwide accepted scientific search engines and databases, including Web of Science, PubMed, Elsevier, ACS, ResearchGate, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). Information was also obtained from local books, PhD. and MSc. Dissertations as well as from Pharmacopeias. FTR has been used as an herbal medicine for centuries in East Asia. A total of 165 chemical compounds have been isolated so far and the main chemical compounds of FTR include alkaloids, terpenoids, flavonoids, phenolic acids, steroids, and phenylpropanoids. Crude extracts, processed products (medicinal slices) and pure components of FTR exhibit a wide range of pharmacological activities such as antitumor, anti-inflammatory, antibacterial, anti-obesity, antioxidant, insecticide, regulating central nervous system (CNS) homeostasis, cardiovascular protection. Furthermore, bioactive components isolated from FTR can induce drug interaction and hepatic injury. Therapeutic potential of FTR has been demonstrated with the pharmacological effects on cancer, inflammation, cardiovascular diseases, CNS, bacterial infection and obesity. Pharmacological and pharmacokinetic studies of FTR mostly focus on its main active alkaloids. Further in-depth studies on combined medication and processing approaches mechanisms, pharmacological and toxic effects not limited to the alkaloids, and toxic components of FTR should be designed. Image 1 [ABSTRACT FROM AUTHOR]

• Betaine reduced the pain response. • Co-injection of the naloxone and betaine decreased anti-nociception effect of the betaine in Formalin and Writhing tests. • Co-administration of the flumazenil and betaine, diminished anti-nociception effect of the betaine. • Betaine decreased MDA and improved GPx and SOD levels in formalin received mice. Pain is a physiological response which is mediated via the central and peripheral nervous system. Betaine, is a methyl glycine derivative and a commonly used nutrient supplement. The main purpose of the current paper is to determine the possible anti-nociceptive and antioxidant activity and sedative effect of betaine in mice. Adult male albino mice were divided into two categories, formalin and writhing tests. In the formalin test, mice were injected with betaine (10, 20 and 30 mg/kg) or morphine (5 mg/kg). For co-injections mice received betaine (30 mg/kg) + naloxone (2 mg/kg) or atropine (1 mg/kg), chlorpheniramine (20 mg/kg), flumazenil (5 mg/kg), cimetidine (12.5 mg/kg) and cyproheptadine (4 mg/kg). Then the formalin test was done and paw licking time was determined. In the writhing test, injections were the same but the animals were injected with acetic acid (0.6 %) and the percentage of writhing inhibition was recorded. At the end of the study, blood antioxidant levels were determined. According to the results, betaine reduced the pain response in a dose-dependent manner. Co-administration of the naloxone + betaine or flumazenil + betaine significantly decreased the anti-nociceptive effect of betaine on the licking and biting time of the injected paw and inhibited the number of writhing movements. Betaine decreased malondialdehyde (MDA) and improved superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in formalin receiving mice. No adverse locomotion and sedation effect were observed in betaine-treated mice. These findings suggest that betaine has anti-nociceptive and antioxidant activity in mice, and its anti-nociceptive role interacts with opioidergic and GABA receptors. [ABSTRACT FROM AUTHOR]