Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products

Introduction. The pathophysiology of functional dyspepsia (FD) remains uncertain, but the interstitial cells of Cajal (ICCs), pacemakers that regulate gastrointestinal motility, are garnering attention as key modulators and therapeutic targets in FD. This review comprehensively discusses the involvement of ICCs in the pharmacologic actions of FD and as therapeutic targets for herbal products for FD. Methods. A search of the literature was performed using PubMed by pairing “interstitial cells of Cajal” with “medicinal plant, herbal medicine, phytotherapy, flavonoids, or traditional Chinese medicine (TCM).” Results. From the 55 articles screened in the initial survey, 34 articles met our study criteria. The search results showed that herbal products can directly depolarize ICCs to generate pacemaker potentials and increase the expression of c-kit and stem cell factors, helping to repair ICCs. Under certain pathological conditions, medicinal plants also protect ICCs from oxidative stress and/or inflammation-induced impairment. Two representative herbal decoctions (Banhasasim-tang, 半夏泻心汤, and Yukgunja-tang, 六君子汤) have been shown to modulate ICC functions by both clinical and preclinical data. Conclusion. This review strongly indicates the potential of herbal products to target ICCs and suggests that further ICC-based studies would be promising for the development of FD treatment agents.

Meta-Assessment of Metformin Absorption and Disposition Pharmacokinetics in Nine Species

The objective of this study was to systematically assess literature datasets and quantitatively analyze metformin PK in plasma and some tissues of nine species. The pharmacokinetic (PK) parameters and profiles of metformin in nine species were collected from the literature. Based on a simple allometric scaling, the systemic clearances (CL) of metformin in these species highly correlate with body weight (BW) (R2 = 0.85) and are comparable to renal plasma flow in most species except for rabbit and cat. Reported volumes of distribution (VSS) varied appreciably (0.32 to 10.1 L/kg) among species. Using the physiological and anatomical variables for each species, a minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue compartments (Tissues 1 and 2) was used for modeling metformin PK in the nine species. Permeability-limited distribution (low fd1 and fd2) and a single tissue-to-plasma partition coefficient (Kp) value for Tissues 1 and 2 were applied in the joint mPBPK fitting. Nonlinear regression analysis for common tissue distribution parameters along with species-specific CL values reasonably captured the plasma PK profiles of metformin across most species, except for rat and horse with later time deviations. In separate fittings of the mPBPK model to each species, Tissue 2 was considered as slowly-equilibrating compartment consisting of muscle and skin based on in silico calculations of the mean transit times through tissues. The well-fitted mPBPK model parameters for absorption and disposition PK of metformin for each species were compared with in vitro/in vivo results found in the literature with regard to the physiological details and physicochemical properties of metformin. Bioavailability and absorption rates decreased with the increased BW among the species. Tissues such as muscle dominate metformin distribution with low permeability and partitioning while actual tissue concentrations found in rats and mice show likely transporter-mediated uptake in liver, kidney, and gastrointestinal tissues. Metformin has diverse pharmacologic actions, and this assessment revealed allometric relationships in its absorption and renal clearance but considerable variability in actual and modeled tissue distribution probably caused by transporter differences.

Overcoming Stress, Hunger, and Pain,: CART Peptide’s Promise

Cocaine- and Amphetamine-Regulated Transcript encodes an eponymous peptide, CARTp, which exerts diverse pharmacologic actions in the central and peripheral nervous systems, as well as in several endocrine organs, including pancreas. Here we review those diverse actions, the physiological relevance of which had remained unestablished until recently. With the identification of a CARTp receptor, GPR160, the physiologic importance and therapeutic potential of CARTp or analogs are being revealed. Not only is the CARTp-GPR160 interaction essential for the circadian regulation of appetite and thirst, but also for the transmission of nerve injury-induced pain. Molecular approaches now are uncovering additional, physiologically relevant actions and the development of acute, tissue-specific gene compromise approaches may reveal even more, physiologically relevant actions of this pluripotent ligand/receptor pair.

Salvadora persica: Nature’s Gift for Periodontal Health

Salvadora persica (SP) extract, displays very valuable biotherapeutic capacities such as antimicrobial, antioxidant, antiparasitic and anti-inflammatory effects. Numerous investigations have studied the pharmacologic actions of SP in oral disease therapies but its promising outcomes in periodontal health and treatment are not yet entirely described. The current study has been planned to analyze the reported effects of SP as a support to periodontal therapy to indorse regeneration and healing. In consort with clinical trials, in vitro investigations show the advantageous outcomes of SP adjunctive to periodontal treatment. Yet, comprehensive supplementary preclinical and clinical investigations at molecular and cellular levels are indispensable to reveal the exact therapeutic mechanisms of SP and its elements for periodontal health and therapy.

Enantioselective Analysis of Mexiletine Using Chromatographic Techniques: A Review

Background: Mexiletine belongs to the β-amino-aryl-ether group of pharmaceutical and applied in the diagnosis of antiarrhythmics, allodynia, and myotonic disorders. In its chemical structure, it possesses a chiral center and practiced in the form of the racemic mixture. The production and accessibility of mexiletine have accompanied with a meaningful development in awareness of its pharmacologic actions. But in clinical arrhythmias and binding experiments on cardiac sodium channels, the (R)-enantiomer of mexiletine is more potent than the (S)-enantiomer. Also, (S)-enantiomer is further active in the diagnosis of allodynia than the (R)-enantiomer. Methods: During the last two decades, chromatographic techniques such as HPLC, and GC coupled with mass spectrometry or field ionization detector was used for the stereoselective analysis of MEX enantiomers. Results: The direct enantioresolution deal with the use of chiral stationary phases (CSPs) with or no pre-derivatization which depend on a chromophoric entity in the racemates whereas indirect HPLC process involved the use of chiral derivatization reagents (CDR) for the synthesis of diastereomeric derivatives of racemates. Different techniques have their strengths and weaknesses. Conclusion: Regulation of enantiomeric purity and estimation of particular enantiomers of drug molecules stays an essential topic for therapeutic, diagnostic, and regulatory uses and to promote a precise assessment of the hazards to human health by false enantiomers. This review aims to offer a systematic survey of the analytical methods (chromatography based) used in the enantioselective analysis of MEX developed in the last two decades (the year 2000 onwards).

Significance of Metformin Use in Diabetic Kidney Disease

Metformin is a glucose-lowering agent that is used as a first-line therapy for type 2 diabetes (T2D). Based on its various pharmacologic actions, the renoprotective effects of metformin have been extensively studied. A series of experimental studies demonstrated that metformin attenuates diabetic kidney disease (DKD) by suppressing renal inflammation, oxidative stress and fibrosis. In clinical studies, metformin use has been shown to be associated with reduced rates of mortality, cardiovascular disease and progression to end-stage renal disease (ESRD) in T2D patients with chronic kidney disease (CKD). However, metformin should be administered with caution to patients with CKD because it may increase the risk of lactic acidosis. In this review article, we summarize our current understanding of the safety and efficacy of metformin for DKD.