The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review discusses plant-based natural product drug discovery and how innovative technologies play a role in next-generation drug discovery.

https://www.mdpi.com/1422-0067/19/6/1578/pdf/1

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

An UHPLC-MS/MS method for simultaneous quantification of gallic acid and protocatechuic acid in rat plasma after oral administration of Polygonum capitatum extract and its application to pharmacokinetics.

Glucosyltransferases (Gtfs) play critical roles in the etiology and pathogenesis of Streptococcus mutans (S. mutans)- mediated dental caries including early childhood caries. Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides (EPSs), the key virulence property in the cariogenic process. Therefore, Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms. Importantly, targeting Gtfs selectively impairs the S. mutans virulence without affecting S. mutans existence or the existence of other species in the oral cavity. Over the past decade, numerous Gtfs inhibitory molecules have been identified, mainly including natural and synthetic compounds and their derivatives, antibodies, and metal ions. These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness. Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies, which is more effective for inhibiting Gtfs than one drug or class of drugs. This review highlights our current understanding of Gtfs activities and their potential utility, and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.

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Molecular mechanisms of inhibiting glucosyltransferases for biofilm formation in Streptococcus mutans.

Emerging threats to human health require a concerted effort in search of both preventive and treatment strategies, placing natural products at the center of efforts to obtain new therapies and reduce disease spread and associated mortality. The therapeutic value of compounds found in plants has been known for ages, resulting in their utilization in homes and in clinics for the treatment of many ailments ranging from common headache to serious conditions such as wounds. Despite the advancement observed in the world, plant based medicines are still being used to treat many pathological conditions or are used as alternatives to modern medicines. In most cases, these natural products or plant-based medicines are used in an un-purified state as extracts. A lot of research is underway to identify and purify the active compounds responsible for the healing process. Some of the current drugs used in clinics have their origins as natural products or came from plant extracts. In addition, several synthetic analogues are natural product-based or plant-based. With the emergence of novel infectious agents such as the SARS-CoV-2 in addition to already burdensome diseases such as diabetes, cancer, tuberculosis and HIV/AIDS, there is need to come up with new drugs that can cure these conditions. Natural products offer an opportunity to discover new compounds that can be converted into drugs given their chemical structure diversity. Advances in analytical processes make drug discovery a multi-dimensional process involving computational designing and testing and eventual laboratory screening of potential drug candidates. Lead compounds will then be evaluated for safety, pharmacokinetics and efficacy. New technologies including Artificial Intelligence, better organ and tissue models such as organoids allow virtual screening, automation and high-throughput screening to be part of drug discovery. The use of bioinformatics and computation means that drug discovery can be a fast and efficient process and enable the use of natural products structures to obtain novel drugs. The removal of potential bottlenecks resulting in minimal false positive leads in drug development has enabled an efficient system of drug discovery. This review describes the biosynthesis and screening of natural products during drug discovery as well as methods used in studying natural products.

The Role of Natural Products as Sources of Therapeutic Agents for Innovative Drug Discovery

Objective: To optimize the conditions for extraction of quercitrin and total flavonoids (TF) from Herba Polygoni Capitati (Touhualiao in Chinese) by using response surface methodology (RSM). Materials and Methods: A central composite design (CCD) was adopted to investigate the effects of three independent variables including solvent composition (%), solvent-material ratio (ml/g) and extraction time (min) on the responses, quercitrin and TF yields. Results: The optimized conditions of the extraction are as follows: Ethanol concentration, 65.63%; solvent-material ratio, 10.55:1 (ml/g); extraction time, 54.33 min. The established mathematical model described the factors of experimental parameters well and provided a statistically accurate prediction of the optimum yields of quercitrin and TF. Conclusion: The experimental values agreed with those predicted by the established mathematical model, thus indicating the suitability of the model employed and the success of RSM in optimizing the extraction conditions.

Optimization of quercitrin and total flavonoids extraction from Herba Polygoni Capitati by response surface methodology.

The invention relates to preparation methods of Chuanxiongchatiao granule extracts and preparations thereof. Specifically, the preparation method of the preparations comprises the following steps: (1) taking the rhizome of chuanxiong, radix angelicae, angelica polyclada, asarum, divaricate saposhnikovia root and liquorice, adding water to decoct the medicines, filtering the decoction and keeping the soup for later use; (2) extracting volatile oils from mint and schizonepeta for later use, filtering the water solution of the volatile oils and merging the filtrate with the soup obtained in the step (1); (3) carrying out nanofiltration on the merged soup obtained in the step (2) with a film, abandoning the dialyzate and spray drying the obtained concentrates to prepare extract powder as the extracts of the preparations; and (4) uniformly doping the volatile oils obtained in the step (2) in the extract powder obtained in the step (3) and then optionally doping pharmaceutically acceptable auxiliary materials uniformly to prepare the preparations. The invention also relates to the extracts and preparations obtained by the methods. The methods have the characteristics of low cost, low possibility of damage of thermosensitive ingredients and the like.

Preparation methods of Chuanxiongchatiao granule extracts and preparations thereof

Effective parts obtained by alcohol extraction of raw materials of Relingqing granules as well as preparation method and applications thereof

The invention relates to relinging extractum and a preparation method and the application, and also relates to a drug composite containing the extractum; in the invention, polygonum capitatum is extracted to prepare the Relinging extractum with water, and activity research is carried out. The relinging extractum has obvious effect on antibiosis, anti-inflammation, analgesia and diuresis and otheraspects.

Relinging extractum and preparation method and application

The invention relates to a novel method for planting polygonum capitatum as a medicinal material of a Relinqing granule. The method specifically comprises the steps of: (1), selecting a cultivated land suitable for the growth of polygonum capitatum; (2), preparing land, namely, deeply ploughing the land for above 30cm before frost comes, and freezing partial pests and harmful microorganisms to death by using low temperature in winter; (3), carrying out lifting of seedlings between the last ten-day period of April to the middle ten-day period of the May; (4), transplanting and planting and filling gaps with seedlings, namely, transplanting in cloudy or rainy days or the afternoons of sunny days between the end of the April and the middle ten-day period of the May, and immediately filling the gaps with the seedlings within one week after transplanting; (5), carrying out field management, at least comprising intertilling and weeding, irrigation and drainage, prevention of water logging, fertilizer application, pest control, interplanting, crop rotation and the like, and carrying out crop rotation with the following plants such as radix pseudostellariae, mint and iris tectorum; (6), harvesting and processing, namely, harvesting from July to October, and processing by adopting manners of drying, airing and drying in the shade. The polygonum capitatum as the medicinal material of the Relinqing granule, planted by adopting the method disclosed by the invention, is capable of generating huge economic benefit and social benefit.

Method for planting polygonum capitatum as medicinal material of Relinqing granule

The invention discloses a method for preparing arctiin. The method mainly comprises the following steps of: extracting a burdock medicinal material with water; filtering the extracting solution, and directly introducing into a macroporous resin column for adsorbing and enriching; eluting gradually with water and an ethanol solution in sequence; collecting the needed eluent, concentrating and filtering; treating with a decoloring resin column to obtain crude arctiin; and crystallizing with a water-containing mixed solvent to obtain a finished product of which the purity is more than 90 percent. The method has the advantages of simple process, continuous operation, convenience in automation, convenience for recycling solvents, low energy consumption, high product purity and easiness for realizing industrial amplification.

Li Menglin

Papers

Preparation methods of Chuanxiongchatiao granule extracts and preparations thereof

Effective parts obtained by alcohol extraction of raw materials of Relingqing granules as well as preparation method and applications thereof

Relinging extractum and preparation method and application

Method for planting polygonum capitatum as medicinal material of Relinqing granule

Method for preparing arctiin