Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 1, 2024

Over 100-1000 microbial species reside in the human gut, where they predominantly influence the host's internal environment and, thus, have a significant impact on host health. Probiotics are best characterized as a microbe or a group of microbes that reside in the gut and support the body's internal microbiota. Probiotics are linked to increased health advantages, including better immune function, improved nutritional absorption, and protection against cancer and heart-related illnesses. Several studies have demonstrated that combining probiotics from different strains with complementary activities may have synergistic advantages and aid in re-establishing the equilibrium of how immunological niches and microorganisms interact. Another thing to remember is that even though a product contains more probiotic strains, that doesn't always guarantee that the health benefits will be more significant. For specific combinations to be justified, there must be clinical proof. The clinical results of a probiotic strain are specifically pertinent to the participants in the relevant research, such as studies on adults or newborn infants. Clinical outcomes of a probiotic strain are mainly connected to the investigated health area (such as gut health, immune health, oral health, etc.). As a result, picking the right probiotic is essential yet tricky because of several factors, including probiotic products with the disease and strain-specific effectiveness exists; however, various probiotic strains have diverse modes of action. The current review focuses on probiotic categorization, their function in enhancing human health, and any potential health benefits of probiotic combinations.

Diabetic nephropathy (DN) is the foremost ailment resulting in end-stage renal damage. Chronic hyperglycaemia and hyperlipidaemia are the foremost reason for disease progression. The disease is characterized by the severity of albuminuria and cardiovascular disorders. Approximately 20 to 40% of the global prevalence of DN is mostly reported to occur in individuals with diabetes, and nearly 28% of DN occurs in individuals with other renal disorders. The pathological mechanism is very complex, involving innumerable targets and leading to multiple pharmacological effects. Thus, the scientific community is forced to work in search of safe and potent therapeutics that can tackle the complex pathology of DN effectively. The secondary plant metabolites categorized as terpenoids gained attention as potential therapeutics contrary to others for the management of diabetic nephropathy and other associated syndromes by their strong antioxidant activity and inhibition of advanced glycation and its associated products. This review focused on herbal therapeutics for the management of diabetic nephropathy. Moreover, different types of terpenoids, their biological sources, and proposed mechanisms of action are explored for the development of a novel pharmacophore for diabetic nephropathy.

Sarcopenia is becoming prevalent in older or inactive patients, which is placing a heavy burden on the social health system. Studies on the pathogenesis of sarcopenia mainly focus on adipose tissue, myoglobin autophagy, and mitochondrial dysfunction. Up to now, non-drug treatment has been the main way to treat sarcopenia, and there are no drugs specially approved for the treatment of sarcopenia. Here, the pathophysiology and treatment methods of sarcopenia have been summarized, and new drugs for sarcopenia to be researched and developed in the future have been prospected.

It is well known that skin lesions are among the most common complications of chronic kidney disease (CKD), which significantly impact the patient's quality of life. Research has demonstrated that gut and skin lesions are closely interconnected and affect each other. This interaction is referred to as the "gut-skin axis" and the intestinal microbiota plays a critical role in this interaction. Changes in gut microbiota composition and function are associated with the development of skin diseases, which are part of the "gut-skin axis". Presently, preliminary results have been demonstrated in basic and clinical research on CKD skin lesions. With further research, the "gut-skin axis" theory can provide new ideas for treating CKD skin lesions and may become a potential treatment target.

Diabetes is a metabolic disorder that has been reported to increase the mortality rate worldwide. About 40 million people across the globe suffer from diabetes, with people living in developing countries being affected the most due to this deadly disease. Although the therapeutic management of hyperglycaemia can treat diabetes, metabolic disorders associated with this disease are a greater challenge in its treatment. Hence, potential strategies to treat hyperglycaemia and its side effects are needed. In this review, we have summarized several therapeutic targets, like dipeptidyl peptidase-4 (DPP-4), glucagon receptor antagonists, glycogen phosphorylase or fructose-1,6- biphosphatase inhibitors, SGLT inhibitors, 11beta-HSD-1 inhibitors, glucocorticoids receptor antagonists, glucose-6-phosphatase and glycogen phosphorylase inhibitors. These targets can help in designing and developing novel antidiabetic agents.

Hibiscus rosa-sinensis (H. rosa-sinensis) has been largely used in traditional medicine. This study aims to review the pharmacological and phytochemical properties of Hibiscus rosa-sinensis L and also summarize the pharmacological, photochemical, and toxicological characteristics of H. rosa-sinensis. The current review focuses on the distribution, chemical content, and main uses of H. rosa-sinensis. Various scientific databases, including ScienceDirect, Scopus, PubMed, Google Scholar, etc., were used. Correct plant names were verified from plantlist.org. The results were interpreted, analyzed, and documented based on bibliographic information. This plant has been frequently used in conventional medicine due to its high concentration of phytochemicals. All its parts contain numerous chemical compounds, such as flavonoids, tannins, terpenoids, anthocyanins, saponins, cyclopeptide alkaloids, and vitamins. More interestingly, the roots of this plant contain glycosides, tannins, phytosterols, fixed oils, fats, flavonoids, saponins, gums, and mucilages. The leaves contain alkaloids, glycosides, reducing sugars, fat, resin, and sterols. The stem contains other chemical compounds, such as sitosterol, teraxeryl acetate, cyclic sterculic, and malvalic acids. Finally, the flowers contain riboflavin, thiamine, apigenidine, oxalic acid, citric acid, quercetin, niacin, pelargonidine, and ascorbic acid. This species has a wide variety of pharmacological applications, such as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, antihypertensive, antifertility, antifungal, anticancer, hair growth-promoting, antihyperlipidemic, reproductive, neurobehavioral, antidepressant, and antipyretic activities. Finally, toxicological studies have shown that higher doses of extracts from the plant are safe.

Background: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases.Objective: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species.Methods: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases.Result: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects.Conclusion: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in

Background: Thyroid nodule (TN) is a highly prevalent clinical endocrine disease. Many countries have formed guidelines on the prevention and treatment of TN based on extensive research. However, there is a scarcity of TN-related literature based on bibliometrics.Objectives: This study aimed to evaluate the scientific achievements and progress of TN research from a global perspective by investigating the literature for 20 years through bibliometrics.Methods: We searched the literature on TN in the core collection of the Web of Science database from 2002 to 2021 and used the Citespace software to analyze the co-authorship, co-citation, and co-occurrence of countries, institutions, authors, keywords, and co-cited literature.Results: We retrieved 12319 documents related to TN. The literature on TN has been growing since 2002. The United States has contributed the largest proportion of TN papers (20.64%), followed by China, Italy, and South Korea. The United States ranked first in terms of centrality (0.38). Haugen BR, Gharib H, and Cibas ES are the top three most cited authors. The papers published in Thyroid were cited most frequently (7952 times). The most prominent keywords were management, cancer, fine needle aspiration, diagnosis, malignant tumor, thyroid cancer, ultrasound, biopsy, benign, surgery, ablation, and cytology. All keywords could be divided into three categories: diagnosis stratification, treatment, and cancer. As far as potential hot spots are concerned, the keywords that have recently burst strongly and are still continuing are: "Association Guideline" (2018-2021), "Radiofrequency Ablation" (2017-2021), "Classification" (2019-2021), and "Data System" (2017-2021).Conclusion: Based on the current trends, the number of publications on TN will continue to increase. The United States is the most active contributor to research in this field. Previous literature focused on stratification, cancer, surgery, and ablation, and there were different opinions on the stratification of diagnosis. There were relatively few studies on pathogenesis and treatment using medicine. More focus will be placed on association guidelines, radiofrequency ablation, classification, and data system, which may be the next popular topics in TN research.

Introduction: Qin medicines are medicinal plants growing in habitat around the peak of Qinling Mountain. Their unique curative effects on bone metabolic diseases and pain diseases have been favoured by the local people in clinical trials for thousands of years. Libanotis buchtormensis (Fisch.) DC. (LBD), is one of the popular Qin herbs, which has been widely used for the treatment of various diseases, such as osteoporosis, rheumatic, and cardiovascular diseases. However, due to the multiple compounds in LBD, the underlying molecular mechanisms of LBD remain unclear.Objective: This study aimed to systemically investigate the underlying mechanisms of LBD against bone diseases.Methods: In this study, a systems pharmacology platform included the potential active compound screening, target fishing, and network pharmacological analysis was employed to decipher the action mechanisms of LBD.Results: As a result, 12 potential active compounds and 108 targets were obtained. Furthermore, compound-target network and target-pathway network analysis showed that multi-components interacted with multi-targets and multi-pathways, i.e., MARK signalling pathway, mTORC1 signalling pathway, etc., involved in the regulation of the immune system and circulatory system. These results suggested the mechanisms of the therapeutic effects of LBD on various diseases through most compounds targeted by multiple targets.Conclusion: In conclusion, we successfully predicted the LBD bioactive compounds and potential targets, implying that LBD could be applied as a novel therapeutic herb in osteoporosis, rheumatic, and cardiovascular diseases. This work provides insight into the therapeutic mechanisms of LBD for treating various diseases.

Background: Thyroid cancer (TC) is a frequent endocrine malignant tumor with various pathologic types. miRNA-363-3p plays a pivotal part in the occurrence, development, prognosis, and treatment of cancer.Objective: To explore the mechanism of miRNA-363-3p in TC and provide a new idea for targeted therapy of TC.Methods: Differential miRNAs and downstream target mRNAs in TC tissues were predicted with bioinformatics analysis. Expression levels of miRNA-363-3p and Synaptotagmin I (SYT1) in TC cells were ascertained by qRT-PCR. Cell migration, invasion, and proliferation were detected by wound healing assay, transwell assay, colony formation assay, CCK-8, and BrdU fluorescence experiment, respectively. Flow cytometry was utilized to detect the levels of apoptosis and necrosis. Immunofluorescence assay was used for detecting autophagosome formation in cells, and the expression levels of autophagy-related proteins, as well as NF-ΚB related proteins, were measured by western blot. Dual-luciferase reporter gene assay was applied for detecting the interaction between miRNA-363-3p and SYT1.Results: miRNA-363-3p was prominently down-regulated in TC cells. miRNA-363-3p overexpression suppressed migration, invasion, and proliferation, promoting apoptosis and necrosis of TC cells. As the downstream target of miRNA-363-3p, SYT1 was up-regulated in TC cells. SYT1 overexpression reversed the inhibition of TC cell proliferation, invasion, migration, and autophagy mediated by miRNA-363-3p overexpression. In addition, miRNA-363-3p overexpression inhibited the activation of the NF-ΚB pathway in cells, while further overexpression of SYT1 weakened the inhibition of miRNA-363-3p overexpression on the NF-ΚB pathway.Conclusion: miRNA-363-3p affected the NF-ΚB signaling pathway by down-regulating SYT1 expression to inhibit the malignant progression of TC cells, providing theoretical support for the treatment of TC.

Background: Diabetic cardiomyopathy (DCM) is the leading cause of diabetic death as the final occurrence of heart failure and arrhythmia. Traditional Chinese medicine is usually used to treat various diseases including diabetes.Objective: This study sought to investigate the effects of Traditional Chinese medicine supplementing Qi and activating blood circulation (SAC) in DCM.Methods: After the construction of the DCM model by streptozotocin (STZ) injection and high glucose/fat diet feeding, rats were administered intragastrically with SAC. Then, cardiac systolic/diastolic function was evaluated by detecting left ventricular systolic pressure (LVSP), maximal rate of left ventricular pressure rise (+LVdp/dtmax), and fall (-LVdp/dtmax), heart rate (HR), left ventricular ejection fraction (EF), LV fractional shortening (FS) and left ventricular end-diastolic pressure (LVEDP). Masson’s and TUNEL staining were used to assess fibrosis and cardiomyocyte apoptosis.Results: DCM rats exhibited impaired cardiac systolic/diastolic function manifested by decreasing LVSP, + LVdp/dtmax, -LVdp/dtmax, HR, EF and FS, and increasing LVEDP. Intriguingly, traditional Chinese medicine SAC alleviated the above-mentioned symptoms, indicating a potential role in improving cardiac function. Masson’s staining substantiated that SAC antagonized the increased collagen deposition and interstitial fibrosis area and the elevations in protein expression of fibrosisrelated collagen I and fibronectin in heart tissues of DCM rats. Furthermore, TUNEL staining confirmed that traditional Chinese medicine SAC also attenuated cardiomyocyte apoptosis in DCM rats. Mechanically, DCM rats showed the aberrant activation of the TGF-β/Smad signaling, which was inhibited after SAC.Conclusion: SAC may exert cardiac protective efficacy in DCM rats via the TGF-β/Smad signaling, indicating a new promising therapeutic approach for DCM.