A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination

The decriminalization of cannabis and the growing interest in cannabinoids as therapeutics require efficient methods to discover novel compounds and monitor cannabinoid levels in human samples and products. However, current methods are limited by the structural diversity of the active compounds. Here, we construct a G-protein coupled receptor-based yeast whole-cell biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three real-life applications. First, we screen a library of compounds to discover two novel agonists and four antagonists and demonstrate that our biosensor can democratize GPCR drug discovery by enabling low-cost high-throughput analysis using open-source automation. Subsequently, we bioprospect 54 plants to discover a novel phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect illicit synthetic drugs like “Spice”/“K2”. Taking advantage of the extensive sensing repertoire of GPCRs, this technology can be extended to detect numerous other compounds.

Novel Effects Associated with the Use of Probiotics, Synbiotics and Prebiotics

To maintain the wellbeing of the human gut, the role of its microflora and their metabolites is fundamental. Probiotics is a Greek term, which is used to define non-living microbes that are beneficial in nature and exert numerous advantages on the host body. The intestinal microflora’s function and activity may also be improved by administering some of the prebiotics (indigestible dietary fibers) independently or in a c combination with probiotics. The term “Synbiotics” is used to denote the combination of both prebiotics and probiotics. It should always be noted that numerous disorders are being associated with the abnormal function of microbiota/microflora that can be regulated and stabilized with the help of ingestion of probiotics, prebiotics or their combination. Multiple benefits are associated with the use of these probiotics, synbiotics and prebiotics including healthier digestive system, proper immune response of the gut and treatment of numerous GI tract disorders. All these issues are encountered because of treatments with new synthetic drugs that affect the digestive system as well as numerous organs in the body. Ulcerative colitis is a term that refers to chronic inflammation of the colon emerging as a result of improper immune response to intestinal microflora of the host. Researchers have studied the effects of synbiotics to treat this chronic condition1. As for the action mechanism of the synbiotics is concerned, it is assumed that they modulate the inflammatory response through expression of the cytokines, probiotic bacteria assisted modulation of the immune cells and prebiotics assisted production of certain short chain fatty acids. Jayanama and Theou studied the consequences of improper ingestion of probiotics and prebiotics in elderly patients. They revealed that physical inactivity, sarcopenia, and polypharmacy could be treated with the help of probiotics, prebiotics or a combination of both2. All the aforementioned disorders can lead to gut dysbiosis. The researchers have also revealed that the gut microbiota homeostasis can be improved with the help of probiotics and prebiotics and they can be a helping hand in the prevention of aging and frailty. It is evident that left and right prescriptions of antibiotics and their use caused antibiotic resistance in the pathogens. This issue can be best resolved with the ingestion of probiotics and prebiotics. The systematic evidence to treat infected chronic wounds has been provided by Brognara et al3. Similarly, chronic wounds and burns treatment is done widely with the use of Lactobacillus plantarum. Some other researchers have reviewed the available data associated with the use of numerous prebiotics in the treatment of idiopathic constipation, and highly prevalent GIT disorrderrs4-6. This is due to the capability of prebiotics to improve the consistency of the stool, bloating and number of bowel movements. A limited data is available regarding the efficacy of prebiotics in the treatment of ulcerative colitis and pouchitis. It is concluded that probiotics, prebiotics and synbiotics have been imparting a role in treating GIT disorders including indigestion, traveler’s diarrhea, IBD etc. Scientific reports have revealed their role in the treatment of cancerous disease, obesity, kidney and brain disorders. Many tools for the research of probiotics, prebiotics and synbiotics are now available; therefore, the future bio-therapeutics are going to be changed with the passage of time.

In Vitro Anti-Diabetic Activities and UHPLC-ESI-MS/MS Profile of Muntingia calabura Leaves Extract

Anti-diabetic compounds from natural sources are now being preferred to prevent or treat diabetes due to adverse effects of synthetic drugs. The decoction of Muntingia calabura leaves was traditionally consumed for diabetes treatment. However, there has not been any published data currently available on the processing effects on this plant’s biological activity and phytochemical profile. Therefore, this study aims to evaluate the effect of three drying methods (freeze-drying (FD), air-drying (AD), and oven-drying (OD)) and ethanol:water ratios (0, 50, and 100%) on in vitro anti-diabetic activities of M. calabura leaves. In addition, an ultrahigh-performance-liquid chromatography–electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was used to characterize the metabolites in the active extract. The FD M. calabura leaves, extracted with 50% ethanol, is the most active extract that exhibits a high α-glucosidase and α-amylase inhibitory activities with IC50 values of 0.46 ± 0.05 and 26.39 ± 3.93 µg/mL, respectively. Sixty-one compounds were tentatively identified by using UHPLC-ESI-MS/MS from the most active extract. Quantitative analysis, by using UHPLC, revealed that geniposide, daidzein, quercitrin, 6-hydroxyflavanone, kaempferol, and formononetin were predominant compounds identified from the active extract. The results have laid down preliminary steps toward developing M. calabura leaves extract as a potential source of bioactive compounds for diabetic treatment.

Applications of lipid-based nanocarriers for parenteral drug delivery

This review describes the use of Lipid-based Nanocarriers (LNCs) for the parenteral delivery of pharmaceutical actives. Firstly, the two generation of LNCs such as ‘‘solid lipid nanoparticles’’ (SLNs) and ‘‘nanostructured lipid carriers’’ (NLCs) are explained in term of preparation, characterization and stability. Although the use of LNCs through parenteral administration has shown many benefits, their use is limited by opsonization, an immune process that causes their short half-life (3-5 min). Therefore, many strategies are discussed to realize “stealth” systems suitable for parenteral administration. Successfully, the requirements and applications of parenteral lipid nanoparticles are reviewed for the delivery of natural compounds, synthetic drugs and genetic materials. In the last period, the latter application has been a remarkable interest due to the numerous benefits of mRNA vaccines to fight the Covid-19 pandemic.

Phytoconstituents in the Management of Covid-19: Demystifying the Fact

The 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and economic burden. COVID-19 created a chaotic situation worldwide and claimed the lives of over 5,027,183 and 248,467,363 confirmed cases have been reported so far as per the data published by WHO (World Health Organization) till 5th November 2021. Scientific communities all over the world are toiling to find a suitable therapeutic drug for this deadly disease. Although till date no promising drug has been discovered for this COVID-19. However, as per the WHO, over 102 COVID-19 vaccines are in clinical development and 185 in pre-clinical development. Naturally occurring phytoconstituents possess considerable chemical richness in the form of anti-viral and anti-parasitic potential and have been extensively exploited for the same globally. Still, phytomedicine-based therapies are considered as the best available treatment option to minimize and treat the symptoms of COVID-19 because of the least possible side effects compared to synthetic drugs recommended by the physicians/clinicians. In this review, the use of plant chemicals as a possible therapeutic agent for severe acute respiratory syndrome coronavirus 2 (SARS CoV2) is highlighted with their proposed mechanism of action, which will prove fruitful and effective in finding a cure for this deadly disease.

Anti-Malarial Drug Resistance

Malaria is a life-threatening infectious disease caused by a protozoan parasite of the genus Plasmodium. It is transmitted through the bites of infected female Anopheles mosquitoes. The global burden is estimated to be around 219 million cases in 87 countries. Natural compounds have been used primarily in the traditional medicine for thousands of years. For the treatment of malaria, natural products were used until the development of synthetic drugs, and most of the currently available anti-malarial drugs have been derived based on the compounds from these traditional medicinal plants. The current chapter tries to briefly indicate the emerging resistance against anti-malarial drugs and to discuss the recent research on natural products that have been evaluated for anti-malarial activity. Rigorous evaluation of the efficacy and safety of traditional medicines is required along with identification of active constituents in order to develop new drugs with novel mechanisms of action.

Application of Nanoemulsion in Tuberculosis Treatment

Tuberculosis is commonly called TB and considered to be the most contagious disease. This disease is caused by a causative agent known as Mycobacterium tuberculosis within the host body cells. Emergence incidence of XDR and MDR of tuberculosis are due to high dose intake and prolonged treatment of antibiotics. In this era, only one vaccine called as BCG is available which is ineffective against infected tuberculosis adults. Though several antibiotics have been produced to overcome drug resistance and even enhance the patient compliance towards treatment and reduce the treatment regimen, we require a novel strategy that can improve the potency of therapeutic synthetic drugs. This approach can be achieved by the application of nanotechnology associated with conventional therapy. Nanotechnology has attributed the promising effects associated with optimized treatment against chronic diseases. This novel technology has the ability to reduce the dose frequency and even resolves the poor patient compliance.

Antidiabetic Activity (Anti-Hyperglycemic Activity, Anti-Hyperlipidemic Activity)/Agents From Medicinal Plants

Diabetes mellitus (DM) is a chronic disease caused by inherited or acquired deficiency in insulin secretion and by decreased insulin secretion by the organ. Insulin deficiency causes the DM. Synthetic drugs are widely used in the treatment of diabetes, but they have some side effects. The antihyperglycemic and antihyperlipedemic effects of the plants are related to their ability to maintain pancreatic function. Medicinal plants constituents such as glycosides, alkaloids, terpenoids, and flavonoids mitigate DM. B. ciliata inhibits the α-glucosidase and α-amylase. Cinnamon extracts improve insulin receptor function by activating insulin receptor kinase and inhibiting insulin receptor phosphatase, which lead to an increase in insulin sensitivity. Morinda lucida also had the highest antioxidant activity, and it also inhibited the α-glucosidase. Many plants have also been shown to antihyperlipedemic effects. Finally, it can be concluded that medicinal plants have that ability to treat or prevent DM.

The Chemical Composition and Health-Promoting Effects of the Grewia Species—A Systematic Review and Meta-Analysis

Globally grown and organoleptically appreciated Grewia species are known as sources of bioactive compounds that avert the risk of communicable and non-communicable diseases. Therefore, in recent years, the genus Grewia has attracted increasing scientific attention. This is the first systematic review which focusses primarily on the nutritional composition, phytochemical profile, pharmacological properties, and disease preventative role of Grewia species. The literature published from 1975 to 2021 was searched to retrieve relevant articles from databases such as Google Scholar, Scopus, PubMed, and Web of Science. Two independent reviewers carried out the screening, selection of articles, and data extraction. Of 815 references, 56 met our inclusion criteria. G. asiatica and G. optiva were the most frequently studied species. We found 167 chemical compounds from 12 Grewia species, allocated to 21 categories. Flavonoids represented 41.31% of the reported bioactive compounds, followed by protein and amino acids (10.7%), fats and fatty acids (9.58%), ash and minerals (6.58%), and non-flavonoid polyphenols (5.96%). Crude extracts, enriched with bioactive compounds, and isolated compounds from the Grewia species show antioxidant, anticancer, anti-inflammatory, antidiabetic, hepatoprotective/radioprotective, immunomodulatory, and sedative hypnotic potential. Moreover, antimicrobial properties, improvement in learning and memory deficits, and effectiveness against neurodegenerative ailments are also described within the reviewed article. Nowadays, the side effects of some synthetic drugs and therapies, and bottlenecks in the drug development pathway have directed the attention of researchers and pharmaceutical industries towards the development of new products that are safe, cost-effective, and readily available. However, the application of the Grewia species in pharmaceutical industries is still limited.

Algae Bioactive Constituents and Possible Role During COVID-19 Pandemic (A review)

Nowadays, the use of natural bio-products in pharmaceuticals is gaining popularity as safe alternatives to chemicals and synthetic drugs. Algal products are offering a pure, healthy and sustainable choice for pharmaceutical applications. Algae are photosynthetic microorganisms that can survive in different environmental conditions. Algae have many outstanding properties that make them excellent candidate for use in therapeutics. Algae grow in fresh and marine waters and produce in their cells a wide range of biologically active chemical compounds. These bioactive compounds are offering a great source of highly economic bio-products. The present review discusses the phytochemical and bioactive compounds present in algae biomass and their potent biological activities. The review focuses on the use of alga in therapy and their pharmaceutical applications with special reference to the possible preventive and therapeutic role of algae against COVID-19.