Current Pharmaceutical Biotechnology - Volume 23, Issue 1, 2022

Gut microbiota (GM), as an organ of the human body, has a particular and autonomous function that is related to it. This review aims to investigate human intestinal and gut microbiota interaction and its impact on health. As a creation referable database about this dynamic and complex organ, several comprehensive projects are implemented by using culture-dependent (culturomics), culture- independent methods (e.g., metagenomics, mathematics model), and Gnotobiological together. This study was done by searching PubMed, Scopus and Google scholar database in the gut, health microbiota, and interaction keywords. The first acquired microbiota during pregnancy or childbirth is colonized in the gut by using specific and non-specific mechanisms. Its structure and shape reach relative stability with selection pressure along with host development until adulthood and keeps its resilience against external or internal variables depending on the host’s genetics and negative feedback. According to research, individuals have 2 functional group microbiotas, including the core (common between vast majorities human) and flexible (transient population) microbiome. The most important role of the GM in the human body can be summarized in three basic landscapes: metabolic, immune system, and gut-brain axis interaction. So, the loss of microbial population balance will lead to disorder and disease.

Background: Active principles from natural sources, in the form of extracts and natural compounds, provide an infinite number of bioactive compounds with consummate disposal of chemical diversity. These compounds and active principles are of utmost importance in the discovery of drugs of biological origin particularly, from plants. Objectives: Development of resourceful technology for the isolation and extraction of bioactive compounds of medicinal importance is considered as an important task for researchers. There are a number of extraction, isolation, and characterization techniques currently utilized; however, most are laborious and use toxic chemicals and huge quantities of raw materials with a very low output. There are a number of abiotic and biotic factors that affects the quality and the quantity of plants bioactive compounds. Considering this, the objectives of the current review are to discuss the various extraction and characterization techniques used to isolate the essential bioactive compounds from three plant species and the biotic and abiotic factors that affect the quantity and quality of the plants secondary metabolites. Methods: Many advanced technologies have been developed and tested for extraction, characterization, and their capacity for high yield products, and those requiring less application of toxic solvents are investigated continuously. Conclusion: In this context, the present review summarizes the different types of extraction and characterization techniques utilized commercially by the food, drug, and pharmaceutical industries for better output and environmentally- and health-benefiting products with special reference to three industrially important plants: Leonotis leonurus (L.) R.Br. (Lamiaceae) and Santalum album L. (Santalaceae) and Aloe vera (L.) Burm. f. (Aloaceae or Asphodelaceae).

Cancer is amongst the leading public health problems globally with continuously increasing prevalence rate that demands for extensive and expensive treatment. Despite availability of number of potential cancer therapies, inadequate success has been achieved due to complexity and heterogeneity of tumors. Moreover, late/ terminal stage cancer leads to multidrug resistance, excruciating side effects, recurrence, etc. This is because of low penetrability and deleterious effects of drug on non-target cells/ tissues. This requires for cost effective, efficacious, alternative/ adjunct, complementary medicines with targeted drug delivery approach. A potential strategy to resolve this difficulty is to use theranostics i.e., formulations having both a therapeutic element and an imaging agent. Phytotherapeutics have been extensively used since times immemorial, having wide acceptability, easy availability, minimal side effects and comparatively inexpensive. These herbal formulations are mostly orally administered and thus subjected to adverse pH, enzymatic degradation, poor gut absorption, low bioavailability and non-targeted delivery that ultimately lead to their poor effectiveness. Constraints associated with conventional phyto-pharmaceuticals can be improved by designing and using “Nano Delivery Systems” (NDS). The foremost aim of metal based NDS is to provide sustained drug release, site-specific action, improved patient’s compliance and enhanced efficacy. Metal Nanocarriers carrying herbal drugs will avoid these obstructions, so the drug can circulate into the blood for a longer period of time and provide optimal amount of the drug to the site of action. Besides, herbal drugs with NDS thus would be efficacious as alternative/ complementary cancer theranostics. Present review describes novel theranostic systems employing metal nanocarriers with diagnostic and therapeutic properties as an effective strategy for cancer treatment. These systems when conjugated with herbal drugs provide an efficient management strategy for cancer.

Underutilized plants are referred to a plant species whose potential is not fully utilized yet and they are usually found abundantly in certain local areas but are globally rare. Sabah is known for high biodiversity and contains many underutilized plants. To our knowledge, this is the first review to provide overview information of the medicinal value and pharmacological properties of underutilized plants in Sabah. Extract and metabolites in different parts of several underutilized plants contain multiple beneficial bioactive compounds and the exploitation of these compounds was supported by additional data that plays various biological activities, including anti-atherosclerotic, anti-cancer antihypercholesterolemic and anti-ulcerogenic. A handful of pharmacological studies on these underutilized plants have conclusively outlined the mode of action in treatment of several diseases and in other health aspects. This paper limits its scope to review and highlight the potential of using underutilized plants in Sabah only which could serve as reliable resource for health product development in pharmaceutical and nutraceutical through continuous discovering of more active and sustainable resources as well as ingredients for food and medicine.

Natural products are well known for their high potency with minimum side effects. Plant extracts are the most commonly used natural products because of their ease of availability and relatively low production cost. Berberine (BBR), a phytochemical component of some Chinese medicinal herbs (most commonly Berberis vulgaris), is an isoquinoline alkaloid with several biological and pharmacological effects including antioxidant, anti-inflammatory, antitumour, antimicrobial, antidepressant, hepatoprotective, hypolipidemic, and hypoglycemic actions. Interestingly, multiple studies have shown that BBR is a potential drug candidate with a multi-spectrum therapeutic application. However, the oral delivery of BBR is challenged owing to its poor bioavailability. Therefore, its oral bioavailability needs to be enhanced before it can be used in many clinical applications. This review provides an overview of the various studies that support the broad range of pharmacological activities of BBR. Also, it includes a section to address the issues and challenges related to the drug and methods to improve the properties of BBR, such as solubility, stability and bioavailability that may be explored to help patients reap the maximum benefit from this potentially useful drug.

Nutritional supplementations are a form of nutrition sources that may help in improving the health complexities of a person throughout his or her life span. Being also categorized as food supplementations, nutraceuticals are products that are extracted from edible sources with medical benefits as well as primary nutritional values. Nutraceuticals can be considered as functional foods. There are evidences that nutraceutical supplementations can alter the commensal gut microbiota and help to prevent or fight against chronic non-communicable degenerative diseases in adults, including neurological disorders (Autism Spectrum Disorder [ASD], Parkinson’s disease [PD], Multiple sclerosis [MS]) and metabolic disorders (Type-II diabetes, obesity and non-alcoholic fatty liver disease). They can even lessen the complexities of preterm babies like extra-uterine growth restriction, necrotizing enterocolitis, infant eczema and allergy (during pregnancy) as well as bronchopulmonary dysplasia. Molecular perception of inflammatory and apoptotic modulators regulating the pathogenesis of these health risks, their control and management by probiotics and prebiotics could further emphasize the scientific overview of their utility. In this study, the pivotal role of nutraceutical supplementations in regulating or modulating molecular pathways in the above non-communicable diseases is briefly described. This work also gives an overall introduction of the sophisticated genome-editing techniques and advanced delivery systems in therapeutic activities applicable under these health risks.

Changes in human lifestyles and environmental deterioration globally cause the emergence of new viruses, posing research challenges. The outburst of COVID-19 (nCoV19) is a recent example, wherein effective management of virus, using the conventional medication and effective diagnostic measures is a challenge. While many ongoing strategies from vaccine development to drug repurposing are currently being investigated, a targeted approach with nanotechnology can be helpful to meet the demand for preventive and diagnostic measures. The significant results of nanotechnology in providing better efficacy of pharmaceutical drugs is expected to combat nCoV19 by using nanotechnology- based solutions, preventive treatment, and diagnosis. This article addresses the dire need for nanotechnology-based solutions in the current pandemic, as well as analyzes the ongoing innovation and existing patents that can be used to provide better solutions. Multiple applications of nanotechnology are considered to be helpful in preventive and diagnostic measures, immune response modulation, and immunity boosters, along with projecting a pathway for industry and academic researchers for addressing such a pandemic.

Cell-free DNA (cfDNA) is present in numerous body fluids and generally blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized method investigating the non-solid biological tissue by revealing circulating cells, cell-free DNA, etc., that enter the body fluids. Since cancer cells disengage from compact tumors circulating in peripheral blood, evaluating cancer patients' blood profile is essential for the molecular level analysis of various tumor-derived constituents. Cell-free DNA samples can deliver a significant diagnosis in oncology, for instance, tumor heterogeneity, rapid tumor development, response to therapy and treatment, comprising immunotherapy, and mechanisms of cancer metastasis. Malignant growth at any phase can cause the occurrence of tumor cells in addition to fragments of neoplasticity. Liquid biopsy indicates diverse blood-based biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA), and exosomes. Cell-free DNAs are little DNA fragments circulating in plasma or serum, just as other fluids present in our body. Cell-free DNA involves primarily double-stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the vesicles' lumen. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or DNA release from the tumor cells into circulation. The evolution of innovations, refinement, and improvement in therapeutics to determine the fragment size of cfDNA and its distribution provide essential information related to pathological conditions of the cell, thus emerging as a promising indicator for clinical output in medical biotechnology.

Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways plays a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by the depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for the prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

Background: Based on the long history of the medicinal use of Thunbergia laurifolia, Clerodendrum disparifolium and Rotheca serrata, the extract formulations of these species: T. laurifolia and C. disparifolium; T. laurifolia and R. serrata; and T. laurifolia, C. disparifolium and R. serrata, called formulas 1, 2 and 3, were created for detoxification testing to take more advantage of each species. Objective: The objective of this study is to estimate the detoxifying effects of studied extract formulations on human cell and tissue culture as a preclinical trial. Methods: The major phytochemicals were derived by GC-MS. The detoxification efficacy of these formulations in cells and DNA levels were derived by MTT and comet assays in toxic PBMCs (incubated with rice whisky or bathroom cleaner). Results: The phytochemical constituents were detected at 23.48% phytol and 43.03% oleamide in T. laurifolia; 12.88% oleamide, 20.93% 9,12,15-octadecatrien, 25.52% squalene, 22.19% butylated hydroxy toluene and 15.36% vitamin E in C. disparifolium; and 30.41% phytol, 32.78% oleamide, and 12.20%, 9,12,15-octadecatrien-1-ol in R. serrata. The toxic cells treated with the plant formulas 1, 2 and 3 showed no IC50 values, but formulas 1 and 2 displayed higher efficacies than formula 3 did. The comet assay indicated that the experiments (the treatment on toxic cells with the plant formulas) induced significant (p < 0.05) DNA damage compared to the negative control due to poisoning occurring before administration of the plant formulas. The OTM of the controls was significantly (p < 0.05) longer than the experimental samples showing significantly reduce the toxicity of the created formulations. Conclusion: The formulas showed high detoxification efficacies and formulations 1 and 2 resulted in higher levels of detoxification than formulation 3, especially in immediate treatment after receiving toxic substances.

Background: Oxymatrine is known as one of the most promising alkaloids from Sophora flavescens for its excellent pharmacological effects. Objective: The aim of this research is to assess the biopharmaceutical and pharmacokinetic activities of oxymatrine and clarify its mechanisms of absorption and metabolism. Methods: The biological characteristics of oxymatrine were systematically investigated by UHPLC-MS/MS. The mechanisms of absorption and metabolism of oxymatrine were further clarified through incubation in rat liver microsomes and transport across the Caco-2 monolayer cell absorption model. Results: It was found that the absolute oral bioavailability of oxymatrine was 26.43%, and the pharmacokinetic parameters Cmax, Tmax, and t1/2 were 605.5 ng/mL, 0.75 h, and 4.181 h after oral administration, indicating that oxymatrine can be absorbed quickly. The tissue distribution tests showed that oxymatrine distributed throughout all the organs, with the small intestine accumulating the highest level, followed by the kidney, stomach, and spleen. The Papp in Caco-2 cell line absorption model was over 1 × 10^-5 and PDR 1.064, and t1/2 of oxymatrine in rat liver microsome in vitro was 1.042 h, indicating that oxymatrine can be absorbed easily through passive diffusion and CYP450 enzymes could be involved in its metabolism. The plasma protein binding rate of oxymatrine was 2.78 ± 0.85%. Conclusion: Oxymatrine can be absorbed into blood easily through passive diffusion, mainly distributed in the intestine, stomach, liver, and spleen in vivo, and CYP450 enzymes in the liver could be involved in its metabolism.

Background and Purpose: Carbon tetrachloride (CCl4) is a dynamic environmental toxin released from chemical factories and its concentration in the atmosphere is accelerating at an alarming proportion. The potential presence of CCl4 in the human body causes liver injury via free radical stimulated inflammatory responses. Objectives: In this study, protective effects of hydromethanolic seeds extract of Prunus persica (PPHM) were evaluated for free radical scavenging potential in CCl4 mediated acute liver toxicity in the murine model. Experimental Approach: Followed by acute oral toxicity analysis, liver cells of Sprague-Dawley (SD) rats were treated with CCl4 and subsequently, the chemoprophylactic effect of extract (400 mg/Kg dose) was evaluated using in vivo studies including, silymarin as the positive control. Biochemical parameters, staining (hematoxylin and eosin (H & E) and Masson’s Trichome) and quantitative gene expression analysis via real-time PCR were used to evaluate hepatic damage control. Results: The results illustrated that PPHM extract exhibit strong anti-oxidant activity, comparable to the positive control, gallic acid. Research study results also demonstrated that the extract treatment at 400 mg/Kg concentration is highly effective in protecting liver damage due to CCl4 exposure. Mechanistic investigations indicated that the therapeutic action of PPHM was correlated with the increase in Nrf2, NQO-1 and decrease in collagen III mRNA genes expression compared to CCl4 treated group. Conclusions and Implications: Accordingly, our research study indicated that PPHM alleviated CCl4-mediated oxidative stress through Nrf2/NQO-1 pathway, thereby protecting liver damage against environmental toxins. Our findings provide supportive evidence to suggest PPHM as a novel nontoxic hepatoprotective agent.