Pharmacohistory of Cannabis Use-A New Possibility in Future Drug Development for Gastrointestinal Diseases.

Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.

Impact of federalization for health financing and workforce in Nepal.

The adoption of its 2015 constitution has converted Nepal to a federal government while simultaneously resulted in significant reforms of the health system in Nepal in terms of both structure and commitment. In this commentary, we review evidence ranging from health financing to health workforce development to show that the impact of federalization on Nepal's health system and its efforts to achieve equitable and affordable universal health care have been mixed. On the one hand, careful efforts of the federal government to support subnational governments during the transition appears to have avoided serious disruption, subnational governments have successfully taken on the financial burden of the health system, and increase subnational control has allowed more flexible adaptation to changing needs than might have otherwise been possible. On the other hand, financing resource and ability disparities across subnational governments contributes to significant disparities in workforce development, and subnational authorities appear to have underestimated significant health issues (e.g. NCDs) in their budgets. We then provide three recommendations to improve the success of the Nepalese system: (1) to assess whether the services covered by health financing and insurance schemes like the National Health Insurance Program adequately address the needs of the rising burden of NCDs in Nepal, (2) to set clear minimum requirements on key metrics for subnational health systems, and (3) to extend grant programs to address resource disparities.

Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components.

The human intestinal commensal microbiota and associated metabolic products have long been regarded as contributors to host health. As the identity and activities of the various members of this community have become clearer, newly identified health-associated bacteria, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Ruminococcus bromii and Roseburia species, have emerged. Notably, the abundance of many of these bacteria is inversely correlated to several disease states. While technological and regulatory hurdles may limit the use of strains from these taxa as probiotics, it should be possible to utilize prebiotics and other dietary components to selectively enhance their growth in situ. Dietary components of potential relevance include well-established prebiotics, such as galacto-oligosaccharides, fructo-oligosaccharides and inulin, while other putative prebiotics, such as other oligosaccharides, polyphenols, resistant starch, algae and seaweed as well as host gut metabolites such as lactate and acetate, may also be applied with the aim of selectively and/or differentially affecting the beneficial bacterial community within the gastrointestinal environment. The present review provides an overview of the dietary components that could be applied in this manner.

Herbal remedies for urinary stones used in India and China: A review.

ETHANOPHARMACOLOGICAL RELEVANCE: The process of formation or appearance of a urinary stone anywhere in the renal tract is known as urolithiasis. It is a longstanding health problem, known to exist since early age of civilization. Records about symptoms, signs and treatment strategies of urinary stones diseases are found in the several ancient texts of traditional medicines such as Ayurveda, Traditional Chinese Medicine (TCM), Siddha and Unani. In Ayurveda, urolithiasis has been considered as one of the eight most troublesome diseases. Ayurvedic management and cure of urinary stone involves herbal formulas, alkaline liquids and surgical procedures. Whereas, TCM recommends polyherbal drugs, acupuncture and mexibustion for treatment of the urinary stones. Among these therapies, herbal remedies are in practice till today for the treatment and cure urinary stone diseases. MATERIALS AND METHODS: A comprehensive review of the scientific literature about pathophysiology of urinary stones and antiurolithiatic plants was undertaken using the following bibliographic databases: MEDLINE/PubMed, Scopus, Web of Knowledge and Google Scholar. The search was conducted from publications from all years until Dec., 2015 by combination of the search terms and Boolean operators; 'urinary stone' OR 'kidney stone' AND 'plant' OR 'medicine' OR 'antiurolithiatic plants'. Outputs were restricted to those completed studies only published in English. In this review, literatures about plants which are used as diuretic and/or in treatment urinary tract infections have not also been considered. The Plant List and Royal Botanical Garden, Kew databases were used to authenticate botanical names of plants. Books and monographs published in English were used to collect information about historical records of antiurolithiatic plants. RESULTS: Recent pharmacological interventions accredited ancient antiurolithiatic claims to several plants and their formulations. The majority of antiurolithiatic plants were found to either dissolve the stones or inhibit the process of urinary stone formation. Plants such as Phyllanthus niruri L. and Elymus repens (L.) Gould, as well as herbal products including 'Wu-Ling-San' formula, 'Cystone' and 'Herbmed' have been proved their utility as promising antiurolithiatic medicines in the different phases of clinical trials. In addition, some of the isolated phytochemicals such as berberine, lupeol, khelin, visnagin, 7-hydroxy-2',4',5'-trimethoxyisoflavone and 7-hydroxy-4'-methoxyisoflavone were reported to have potent antiurolithiatic activity. CONCLUSION: In ancient medicinal texts, antiurolithiatic potential has been ascribed to several plants and their formulations. Present scientific studies provide scientific evidences for few of these claims however, they are insufficient to establish many of these plants and herbal formulations as therapeutic remedies for the treatment and management of urinary stones. Conversely, findings of pre-clinical and clinical studies about some plants and herbal formulations are promising, which underlines the utility of herbal remedies as alternative medicines for the treatment and management of urinary stones in the future.

Essential oils have different effects on human pathogenic and commensal bacteria in mixed faecal fermentations compared with pure cultures.

A static batch culture system inoculated with human faeces was used to determine the influence of essential oil compounds (EOCs) on mixed faecal microbiota. Bacteria were quantified using quantitative PCR of 16S rRNA genes. Incubation for 24 h of diluted faeces from six individuals caused enrichment of Bifidobacterium spp., but proportions of other major groups were unaffected. Thymol and geraniol at 500 p.p.m. suppressed total bacteria, resulting in minimal fermentation. Thymol at 100 p.p.m. had no effect, nor did eugenol or nerolidol at 100 or 500 p.p.m. except for a slight suppression of Eubacterium hallii. Methyl isoeugenol at 100 or 500 p.p.m. suppressed the growth of total bacteria, accompanied by a large fall in the molar proportion of propionate formed. The relative abundance of Faecalibacterium prausnitzii was unaffected except with thymol at 500 p.p.m. The ability of EOCs to control numbers of the pathogen Clostridium difficile was investigated in a separate experiment, in which the faecal suspensions were amended by the addition of pure culture of C. difficile. Numbers of C. difficile were suppressed by thymol and methyl isoeugenol at 500 p.p.m. and to a lesser extent at 100 p.p.m. Eugenol and geraniol gave rather similar suppression of C. difficile numbers at both 100 and 500 p.p.m. Nerolidol had no significant effect. It was concluded from these and previous pure-culture experiments that thymol and geraniol at around 100 p.p.m. could be effective in suppressing pathogens in the small intestine, with no concern for beneficial commensal colonic bacteria in the distal gut.

Sensitivity of pathogenic and commensal bacteria from the human colon to essential oils.

The microbiota of the intestinal tract plays an important role in colonic health, mediating many effects of dietary components on colonic health and during enteric infections. In the context of the increasing incidence of antibiotic resistance in gut bacteria, complementary therapies are required for the prevention and treatment of enteric infections. Here we report the potential application of essential oils (EO) and pure EO compounds to improve human gut health. Nerolidol, thymol, eugenol and geraniol inhibited growth of the pathogens Escherichia coli O157 : H7(VT(-)), Clostridium difficile DSM1296, Clostridium perfringens DSM11780, Salmonella typhimurium 3530 and Salmonella enteritidis S1400 at a half-maximal inhibitory concentration (IC(50)) varying from 50 to 500 p.p.m. Most EO showed greater toxicity to pathogens than to commensals. However, the beneficial commensal Faecalibacterium prausnitzii was sensitive to EO at similar or even lower concentrations than the pathogens. The EO showed dose-dependent effects on cell integrity, as measured using propidium iodide, of Gram-positive bacteria. These effects were not strongly correlated with growth inhibition, however, suggesting that cell membrane damage occurred but was not the primary cause of growth inhibition. Growth inhibition of Gram-negative bacteria, in contrast, occurred mostly without cell integrity loss. Principal component analysis showed clustering of responses according to bacterial species rather than to the identity of the EO, with the exception that responses to thymol and nerolidol clustered away from the other EO. In conclusion, the selective effects of some EO might have beneficial effects on gut health if chosen carefully for effectiveness against different species.

HMC05, Herbal Formula, Inhibits TNF-α-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells.

Vascular inflammation has been implicated in the progression of cardiovascular diseases such as atherosclerosis. In the present study, we found that HMC05, an extract from eight different herbal mixtures, dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced adhesion of monocytes to endothelial cells. Such inhibitory effect of HMC05 correlated with suppressed expression of monocyte chemoattractant protein-1, CC chemokine receptor 2, vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1. In addition, HMC05 significantly inhibited production of reactive oxygen species (ROS) and nuclear factor (NF)-κB activation by TNF-α. Those inhibitory effects of HMC05 (1-10 µg mL(-1)) on the TNF-α-induced inflammatory event was similar to those of berberine (1-10 µM), which is a major component of HMC05 and one of herbal compounds known to have vasorelaxing and lipid-lowering activities. However, berberine significantly reduced the viability of HUVECs in a time- and concentration-dependent manner. In contrast, HMC05 (1-10 µg ml(-1)) did not affect the cell viability for up to 48 h treatment. In conclusion, we propose that HMC05 may be a safe and potent herbal formula against vascular inflammation, and its action may be attributable to the inhibition of ROS- and NF-κB-dependent expression of adhesion molecules and chemokines.

Inhibitory effects of an aqueous extract of Cornus kousa Burg. leaves on TNF-alpha-induced chemokine expression and monocyte adhesion to human colonic epithelial cells.

An aqueous extract of Cornus kousa Burg. leaves (ACK) that contained high amount of polyphenols showed significant antioxidant activity against diphenylpicrylhydrazyl (DPPH) radicals and TNF-alpha-generated reactive oxygen species. ACK at concentrations of 10 and 50 microg/mL significantly inhibited TNF-alpha-induced adhesion of U937 pre-monocytic cells to HT-29 colon epithelial cells in a concentration-dependent manner. The reduced adhesion by ACK correlated with the suppressed expressions of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, the major inflammatory bowel disease (IBD)-associated chemokines. Moreover, ACK significantly suppressed TNF-alpha-induced translocation of redox-sensitive nuclear factor (NF)-kappaB as well as degradation of cytosolic I-kappaBalpha. The effective concentrations of ACK were much lower than that of 5-aminosalicylic acid (3.06 mg/mL), which is an active metabolite of sulfasalazine, a well-known drug used in the treatment of IBD. The results indicate that ACK may provide a potential benefit for the prevention and treatment of inflammatory diseases such as IBD.