Current Pharmaceutical Biotechnology - Volume 23, Issue 13, 2022

The use of herbal medicines and supplements in the last thirty years has increased enormously. Herbal medication has demonstrated promising and effective potential against various diseases. Herbal and phytoconstituent medications are gaining popularity globally and many people are adopting herbal remedies to deal with different health issues. The indiscriminate use of antibiotics, due to the development of antimicrobial resistance, poses an unprecedented problem for human civilization. Bacterial infections are difficult to cure because of the propensity of microbes to acquire resistance to a wide range of antimicrobial drugs. New compounds are being explored and quantified for possible antibacterial activity with little or no side effects. Researchers are investigating the range of therapeutic plants mentioned in Unani, Ayurveda, and Siddha around the globe. Known and commonly acclaimed global databases such as PubMed, Research Gate, Science Direct, Google Scholar were searched using different search strings such as Indian medicinal plants, multidrug resistance (MDR), thin layer chromatography (TLC), antimicrobials, and Synergism were used in diverse combinations to reclaim numerous citations associated with this area. Thus, the current review aims to shed a light on the information of medicinal plants as a potential foundation of herbal drugs and elucidate how synergism and TLC bioautography play a crucial role in finding antimicrobial compounds.

The traditional process of separating and purifying bioactive peptides is laborious and time-consuming. Using a traditional process to identify is difficult, and there is a lack of fast and accurate activity evaluation methods. How to extract bioactive peptides quickly and efficiently is still the focus of bioactive peptides research. In order to improve the present situation of the research, bioinformatics techniques and peptidome methods are widely used in this field. At the same time, bioactive peptides have their own specific pharmacokinetic characteristics, so computer simulation methods have incomparable advantages in studying the pharmacokinetics and pharmacokineticpharmacodynamic correlation models of bioactive peptides. The purpose of this review is to summarize the combined applications of bioinformatics and computer simulation methods in the study of bioactive peptides, concentrating on the role of bioinformatics in simulating the selection of enzymatic hydrolysis and precursor proteins, activity prediction, molecular docking, physicochemical properties, and molecular dynamics. Our review shows that new bioactive peptide molecular sequences with high activity can be obtained by computer-aided design. The significance of the pharmacokinetic-pharmacodynamic correlation model in the study of bioactive peptides is emphasized. Finally, some problems and future development potential of bioactive peptides binding new technologies are being prospected.

Cancer is the uncontrolled proliferation of cells that involves accumulation of genetic mutations by different types of mutagens including physical, chemical, and biological. Consequently, normal cell cycles get interrupted. Immunological assays, histopathological tests, polymerase chain reaction, computed tomography, magnetic resonance, and radiation therapy are some conventional techniques for cancer diagnostics. However, these techniques are not only expensive, time-consuming, tedious but also toxic to healthy cells. Therefore, these limitations are overcome by nanodevices that show high sensitivity, selectivity, rapidity, and cost-effectiveness in the detection of cancer biomarkers. Electrochemical biosensors are more efficient in the early diagnosis of cancers that help in patients' effective and timely treatment. Distinct types of nanotools viz. inorganic, organic, and polymeric nanomaterials are used in cancer therapeutics. Nano approaches have shown many advantages: they are site-specific, require meager amounts of drugs, limited toxicity, avoid drug resistance, and are more efficient, sensitive, and reliable. Therefore, future research should focus on developing highly inventive nanotools for the diagnosis and therapeutics of cancers.

Colorectal cancer (CRC) is the third most prevalent malignant neoplasm in the world. CRC is influenced by both environmental and genetic factors. Through toxin-mediated DNA damage and the promotion of persistent dysregulated inflammation, the gut microbiota plays a crucial role in the development of CRC. In this review, we discussed the correlation between the bacterial microbiota and CRC carcinogenesis as well as the mechanism by which Streptococcus bovis/gallolyticus, Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli can cause CRC.

Background: The development of advanced treatment of triple-negative breast cancer (TNBC) is the utmost need of an era. TNBC is recognized as the most aggressive, metastatic cancer and the leading cause of mortality in females worldwide. The lack of expression of triple receptors namely, estrogen, progesterone, and human epidermal receptor 2 defined TNBC. Objective: The current review introduced the novel biomarkers such as miRNA and family, PD1, EGFR, VEGF, TILs, P53, AR and PI3K, etc. contributed significantly to the prognosis and diagnosis of TNBC. Once diagnosed, the advanced utilization approaches are available for TNBC because of the limitations of chemotherapy. Novel approaches include lipid-based (liposomes, SLN, NLC, and SNEDDS), polymer-based (micelle, nanoparticles, dendrimers, and quantum dots), advanced nanocarriers such as (exosomes, antibody and peptide-drug conjugates), and carbonbased nanocarriers (Carbon nanotubes, and graphene oxide). Lipid-based delivery is used for excellent carriers for hydrophobic drugs, biocompatibility, and lesser systemic toxicities than chemotherapeutic agents. Polymer-based approaches are preferred over lipids for providing longer circulation time, nanosize, high loading efficiency, high linking, avoiding the expulsion of drugs, targeted action, diagnostic and biosensing abilities. Advanced approaches like exosomes, conjugated moieties are preferred over polymeric for possessing potency, high penetrability, biomarkers, and avoiding the toxicity of tissues. Carbon-based gained wide applicability for their unique properties like a versatile carrier, prognostic, diagnostic, sensing, photodynamic, and photothermal characteristics. Conclusion: The survival rate can be increased by utilizing several kinds of biomarkers. The advanced approaches can also be significantly useful in the prognosis and theranostic of triplenegative breast cancer. One of the biggest successes in treating with nanotechnology-based approaches is the marked reduction of systemic toxicity with high therapeutic effectiveness compared with chemotherapy, surgery, etc. The requirements such as prompt diagnosis, longer circulation time, high efficiency, and high potency can be fulfilled with these nanocarriers.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and recently has become a serious global pandemic. Age, gender, and comorbidities are known to be common risk factors for severe COVID-19 but are not enough to fully explain the magnitude of their effect on the risk of severity of the disease. Single nucleotide polymorphisms (SNPs) in several genes have been reported as a genetic factor contributing to COVID-19 severity. This comprehensive review focuses on the association between SNPs in four important genes and COVID-19 severity in a global aspect. We discuss a total of 39 SNPs in this review: five SNPs in the ABO gene, nine SNPs in the angiotensin-converting enzyme 2 (ACE2) gene, 19 SNPs in the transmembrane protease serine 2 (TMPRSS2) gene, and six SNPs in the toll-like receptor 7 (TLR7) gene. These SNPs data could assist in monitoring an individual’s risk of severe COVID-19 disease, and therefore personalized management and pharmaceutical treatment could be planned in COVID-19 patients.

Background: Atherosclerosis (AS) remains prevalent despite hyperlipidemia-lowering therapies. Although multiple functions of miR-199b-5p have been implicated in cancers, its role in endothelial apoptosis and AS remains unclear. This study aimed to examine the role of miR-199b-5p in mitochondrial dynamics and endothelial apoptosis. Methods: Human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) were subjected to other treatments, followed by a series analysis. We found that ox-LDL-treated HUVECs were associated with miR-199b-5p downregulation, increased reactive oxygen species level, reduced adenosine triphosphate (ATP) production, mitochondrial fission, and apoptosis, whereas enhanced miR-199b-5p expression or applied mitochondrial division inhibitor 1 (Mdivi-1) markedly reversed these changes. Results: Mechanistically, A-kinase anchoring protein 1 (AKAP1) was confirmed as a downstream target of miR-199b-5p by dual-luciferase activity reporter assay. AKAP1 overexpression reversed the anti-apoptotic effects of miR-199b-5p through the enhanced interaction of AKAP1 and dynamin protein 1 (DRP1) in ox-LDL–treated HUVECs. Moreover, miR-199b-5p downregulation, AKAP1 upregulation, and excessive mitochondrial fission were verified in human coronary AS endothelial tissues. Conclusion: The miR-199b-5p-dependent regulation of AKAP1/DRP1 is required to inhibit hyperlipidemia- induced mitochondrial fission and endothelial injury and may be a promising therapeutic target for AS.

Background: Appropriate substituents in the galloyl group could lead to significant biological properties. Objectives: Novel galloyl-substituted compounds bearing 2-substituted-1, 3, 4-oxadiazol-5-yl, 5- substituted-1,2,4-triazol-3-yl, and carboxamide groups were synthesized and evaluated for their antiproliferative activity. Additionally, galloyl hydrazide (2) was evaluated by performing cytotoxicity, membrane integrity, cell cycle, and apoptosis assays in HepG2/C3A cells. Methods: General procedure was used for the synthesis of galloyl-substituted (3-9, 11) and characterized by their spectroscopic data (1H and 13C NMR). The antiproliferative activity of all novel galloyl derivatives was evaluated against nine human tumors and one nontumoral cell line. Three response parameters (GI50, TGI, and LC50) were calculated. The cytotoxicity test was performed for the resazurin assay. The membrane integrity, cell cycle, and apoptosis assays were performed by flow cytometry. Results: The substitution of the methoxy group of the galloyl ring system for a carboxamide group (3, 4, 5, and 6) produced compounds with moderate antitumoral activity, particularly 6, against six human cancer cell lines, K-562, PC-3, NCI-ADR/RES, OVCAR, 786-0 and NCI-H460, with GI50 values ≤ 9.45 μg/mL. Triazole derivatives 7 and 8 exhibited higher antitumoral activity toward OVCAR, MCF-7 and leukemia K-562 cell lines, exhibiting GI50 values less than 10 μg/mL. Compound 11 displayed significant activity against PC-3 (GI50 = 4.31 μg/mL), OVCAR (GI50 = 8.84 μg/mL) and K-562 (GI50 = 8.80 μg/mL) cell lines. Galloyl hydrazide (2) had cytotoxic activity in HepG2/C3A cells (IC50 = 153.7 μg/mL). In membrane permeability, cell count, cell cycle, and apoptosis assays, as determined using the IC50 of compound (2) in HepG2/C3A cells, increased membrane permeability, decreased cell count, altered cell cycle, and initial apoptosis was observed compared to the control group. Conclusion: Thus, our results showed for the first time the synthesis, antiproliferative activity, and cytotoxicity of galloyl-substituted compounds. Galloyl-substitution does not have a very strong synergistic effect in the inhibition of cancer cell proliferation compared with galloyl hydrazide (2). Compound 2 demonstrated promising activity in HepG2/C3A hepatocarcinoma cells.