Quantitative Systems Pharmacology: Lessons from Fumaric acid and Herbal Remedies

Abstract

Fumaric acid esters, now often used for treatment of psoriasis and multiple sclerosis, have been identified as bioactive constituents of Fumaria indica used in traditionally known system of medicine as a liver tonicor for treatments of diverse inflammatory conditions, itches and pain. Observations made during efforts to quantify their roles in therapeutically interesting bioactivity profiles of its extracts strongly suggest that their hydrolysis inside the digestive tract to fumaric acid are involved in their protective effects stress triggered alteration in growth rates and behavior of laboratory rodents. They also reaffirm that repeated daily low oral dose studies is necessary for deciphering the roles of fumaric acid or other food chemicals with bactericidal activities, in quantitative systems phytopharmacology of therapeutically used herbal extracts. Our current knowledge on low dose pharmacology of some such phytochemicals commonly consumed with every day meals, or with herbal remedies, is summarized in this report. Aim of this overview is to point out the necessity of better understanding of quantitative systems pharmacology of food phytochemical not only for more rational medicinal uses of traditionally known herbal remedies, but also for increasing the possibility of success in drug discovery and development ventures. Potential uses of bioassays procedures evolving from efforts to better understand quantitative systems pharmacology of fumarates and other food phytochemicals for such purposes are also suggested.

Triethylene glycol-like effects of Ashwagandha (Withania somnifera (L.) Dunal) root extract devoid of withanolides in stressed mice

“…[27-29] Analogous were also the observations made with several other phytochemicals encountered in Withania somnifera extracts as well. [2330] Since only 3.3-mg/kg daily oral doses of WFWS afforded almost complete protection against stress triggered in body weight loss and alteration in thermoregulatory process and compulsive behavior, it seems reasonable to assume that TEG-like bioactive substances other than withanolides are also involved in traditionally known medicinal uses of Ashwagandha and diverse types of Withania somnifera root extract currently commercialized or prepared for research purpose.…”

“…[61] Therefore, it seems to be a particularly well suited not only for better understanding of biological and pharmacological aspects behind Rasayana therapies but also for better understanding of the role of gut microbiota in systems pharmacology of many plants and plant-derived drugs, paradoxical effects of many of which in regulating brain functions have often been reported. [62] Therefore, an effort to better define Ayurvedic system pharmacology of Ashwagandha using the more holistic experimental strategy used in this and our earlier studies[23] can be warranted.…”

“…[14] These observations, taken together with our earlier ones made with structurally diverse bactericidal phytochemicals and some plant-derived drugs, [15-21] led us to the working hypothesis that their modulating effects on gut microbiota composition and functions may also contribute to therapeutically interesting bioactivity profiles of Withania somnifera -like adaptogenic herbs often used in Rasayana therapies or as herbal remedies. [2223] Results of an exploratory experiment added further preclinical evidence in favor of this working hypothesis and suggested that combinations of microbicidal substances other than withanolides are also involved in the traditionally known and more recently, rediscovered medicinal uses of Withania somnifera roots. This experiment was conducted in the realm of our psychopharmacological studies with extracts and bioactive constituents of Ayurvedic Rasayana drugs[24] currently often used for the treatment of obesity and diabetes associated physical and mental health problems.…”

Study of Organic Acids Profile of Genus Persicaria Mill Species

“…Столь широкий спектр фармакологической активности объясняет интерес российских и зарубежных авторов к изучению качественного и количественного содержания ОК в растениях [1,[14][15][16]. Однако, несмотря на весомый список положительных эффектов ОК, существуют и негативные.…”