Gut microbiota in phytopharmacology: A comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions.

The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of gut microbial regulation of intestinal immunometabolic and redox homeostasis have evolved mainly out of in vivo studies associated with high-fat feeding induced metabolic diseases. Techniques utilizing fecal transplantation and germ-free mice have been instrumental in reproducibly demonstrating how the gut microbiota affects disease pathogenesis. However, the pillars of modern drug discovery i.e. evidence-based pharmacological studies critically lack focus on intestinal microflora. This is primarily due to targeted in vitro molecular-approaches at cellular-level that largely overlook the etiology of disease pathogenesis from the physiological perspective. Thus, this review aims to provide a comprehensive understanding of the key notions of intestinal microbiota and dysbiosis, and highlight the microbiota-phytochemical bidirectional interactions that affects bioavailability and bioactivity of parent phytochemicals and their metabolites. Potentially by focusing on the three major aspects of gut microbiota i.e. microbial abundance, diversity, and functions, I will discuss phytochemical-microbiota reciprocal interactions, biotransformation of phytochemicals and plant-derived drugs, and pre-clinical and clinical efficacies of herbal medicine on dysbiosis. Additionally, in relation to phytochemical pharmacology, I will briefly discuss the role of dietary-patterns associated with changes in microbial profiles and review pharmacological study models considering possible microbial effects. This review therefore, emphasize on the timely and critically needed evidence-based phytochemical studies focusing on gut microbiota and will provide newer insights for future pre-clinical and clinical phytopharmacological interventions.

Minocycline as a promising therapeutic strategy for chronic pain.

Chronic pain remains to be a clinical challenge due to insufficient therapeutic strategies. Minocycline is a member of the tetracycline class of antibiotics, which has been used in clinic for decades. It is frequently reported that minocycline may has many non-antibiotic properties, among which is its anti-nociceptive effect. The results from our lab and others suggest that minocycline exerts strong analgesic effect in animal models of chronic pain including visceral pain, chemotherapy-induced periphery neuropathy, periphery injury induced neuropathic pain, diabetic neuropathic pain, spinal cord injury, inflammatory pain and bone cancer pain. In this review, we summarize the mechanisms underlying the analgesic effect of minocycline in preclinical studies. Due to a good safety record when used chronically, minocycline may become a promising therapeutic strategy for chronic pain in clinic.

Derivatives of furanditerpenes from Pterodon genus: Pharmacological studies disclose their potential as chronic pain relief in mice.

Pterodon genus fruits are commercially available at the Brazilian medicinal market used in folk medicine due to their anti-inflammatory, analgesic, and anti-rheumatic effects. Previous studies demonstrated that furanditerpenes possessing vouacapan skeleton, isolated from Pterodon genus, possess expressive antinociceptive activities, with promising moiety for the development of new analgesic products. The antinociceptive properties of compounds 6α,7ß-6α-hidroxivouacapan-7ß-17ß-lactone (HVL) and 6α-oxovouacapan-7ß-17ß-lactone (OVL), semi-synthetic analogues of furanditerpenes previously reported as analgesic agents were evaluated on animal experimental models (Spindola et al., 2010, 2011). The chemical-induced pain methods used in the present work, demonstrated for the first time that both compounds HVL and OVL have potential as important templates for the development of chronic pain control drugs. The main findings of this work were that both compounds were: effective in the writhing test; reduced paw edema in the carrageenan test; effective in the inflammatory phase of the formalin test corroborating their activity against inflammatory pain conditions; effective on reducing pain through the stimulation of vanilloid receptors sensible to capsaicin (an important pathway for chronic pain maintenance); reduced the pain stimulus caused by PGE2 injection (a pathway involved in chronic pain hypersensitivity); effective on decreasing mechanical allodynia in the CFA-model, demonstrating their potential use against chronic pain disorders.

TEMPO-oxidized Konjac glucomannan as appliance for the preparation of hard capsules.

TEMPO-oxidized Konjac glucomannan (OKGM) was developed as new material for preparing vegetarian hard capsules. OKGM of different degrees of oxidation: DO30%, DO50%, and DO80% were prepared to select optimum DO for capsule formation. FT-IR results proved that the primary alcohol groups on KGM were oxidized into carboxyl groups. XRD analysis suggested that TEMPO-oxidation decreased the crystallinity of KGM. DO80% was considered as the optimum candidate for capsule preparation owing to its superior solubility, transparency and reduced viscosity. The hydrophilicity of OKGM films, measured by contact angle measurement, increased with increasing DO. The elongation at break and tensile strength of the OKGM films enhanced with increasing DO. In vitro drug dissolution profile of OKGM capsules showed that the shell rupture time of DO80% capsule is about 5-10 min, and 80% of the drugs were released within 30-45 min. Thus DO80% OKGM was qualified to be used for gastric soluble hard capsules.

Low dose aspirin like analgesic and anti-inflammatory activities of mono-hydroxybenzoic acids in stressed rodents.

AIMS: To compare analgesic and anti-inflammatory activities of aspirin and mono-hydroxybenzoic acids after their daily oral doses. MAIN METHODS: Efficacies of repeated daily stress response suppressing low oral doses (20mg/kg) of aspirin and 2-, 3-, and 4-hydroxybenzoic acids in mice hot plate test for centrally acting analgesics, and in acetic acid induced writing test were compared. Effects of their same daily doses and treatment regimen in cotton pellet granuloma and carrageenan edema test for anti-inflammatory drugs in stressed rats were compared in a second experiment. Effects of treatments on body weights, basal rectal temperatures, organ weights and plasma glucose, insulin and cortisol levels in stressed animals were compared also. KEY FINDINGS: Although stress response suppressing effects of aspirin and all the three hydroxybenzoic acids in both mice and rats were almost equal, effectiveness of 3- and 4-hydroxybenzoic acids as analgesic and anti-inflammatory agents were lower than those of aspirin or salicylic acid. SIGNIFICANCE: Observations made after single oral doses of aspirin or of mono-hydroxybenzoic acids are not very reliable predictors of their pharmacologically interesting bioactivity profiles and efficacies. Prostaglandin synthesis inhibition is not involved in low dose anti-inflammatory activities of 3- and 4-hydroxybenzoic acids. After their repeated daily low oral doses they are almost as potent stress response desensitizers as aspirin or salicylic acid.