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Sirtuins are a family of NAD+ III-dependent histone deacetylases that consists of seven family members, Sirt1-Sirt7, which regulate various signalling pathways and are involved in many critical biological processes of kidney diseases. Traditional Chinese medicine (TCM), as an essential part of the global healthcare system, has multi-component and multi-pathway therapeutic characteristics and plays a role in preventing and controlling various diseases. Through ongoing collaboration with modern medicine, TCM has recently achieved many remarkable advancements in theoretical investigation, mechanistic research, and clinical applications related to kidney diseases. Therefore, a comprehensive and systematic summary of TCM that focuses on sirtuins as the intervention target for kidney diseases is necessary. This review introduces the relationship between abnormal sirtuins levels and common kidney diseases, such as diabetic kidney disease and acute kidney injury. Based on the standard biological processes, such as inflammation, oxidative stress, autophagy, mitochondrial homeostasis, and fibrosis, which are underlying kidney diseases, comprehensively describes the roles and regulatory effects of TCM targeting the sirtuins family in various kidney diseases.

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

Podocyte injury is a major cause of proteinuria in kidney diseases, and persistent loss of podocytes leads to rapid irreversible progression of kidney disease. Sirtuins, a class of nicotinamide adenine dinucleotide-dependent deacetylases, can promote DNA repair, modify transcription factors, and regulate the cell cycle. Additionally, sirtuins play a critical role in renoprotection, particularly against podocyte injury. They also have pleiotropic protective effects on podocyte injury-related glomerular diseases, such as improving the immune inflammatory status and oxidative stress levels, maintaining mitochondrial homeostasis, enhancing autophagy, and regulating lipid metabolism. Sirtuins deficiency causes podocyte injury in different glomerular diseases. Studies using podocyte sirtuin-specific knockout and transgenic models corroborate this conclusion. Of note, sirtuin activators have protective effects in different podocyte injury-related glomerular diseases, including diabetic kidney disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, and lupus nephritis. These findings suggest that sirtuins are promising therapeutic targets for preventing podocyte injury. This review provides an overview of recent advances in the role of sirtuins in kidney diseases, especially their role in podocyte injury, and summarizes the possible rationale for sirtuins as targets for pharmacological intervention in podocyte injury-related glomerular diseases.

Podocyte injury is a common cause of proteinuric kidney diseases. Uncontrollable progressive podocyte loss accelerates glomerulosclerosis and increases the risk of end-stage renal disease. To date, owing to the complex pathological mechanism, effective therapies for podocyte injury have been limited. Accumulating evidence supports the indispensable role of autophagy in the maintenance of podocyte homeostasis. A variety of natural compounds and their derivatives have been found to regulate autophagy through multiple targets, including promotes nuclear transfer of transcription factor EB and lysosomal repair. Here, we reviewed the recent studies on the use of natural compounds and their derivatives as autophagy regulators and discussed their potential applications in ameliorating podocyte injury. Several known natural compounds with autophagy-regulatory properties, such as quercetin, silibinin, kaempferol, and artemisinin, and their medical uses were also discussed. This review will help in improving the understanding of the podocyte protective mechanism of natural compounds and promote their development for clinical use.

Background: The pathogenesis and treatment of cardiovascular disease mediated by chronic kidney disease (CKD) are key research questions. Specifically, the mechanisms underlying the cardiorenal protective effect of Yiqi–Huoxue–Jiangzhuo formula (YHJF), a traditional Chinese herbal medicine, have not yet been clarified. Methods: A classical CKD mouse model was constructed by 5/6 nephrectomy (Nx) to study the effects of YHJF intervention on 5/6 Nx mice cardiorenal function, gut microbial composition, gut-derived metabolites, and NLRP3 inflammasome pathways. Results: YHJF improved cardiac dysfunction and reversed left ventricular hypertrophy, myocardial hypertrophy, and interstitial fibrosis in 5/6 Nx mice. In addition, YHJF inhibited activation of the NLRP3 inflammasome and downregulated the expression of TNF-α and IL-1β both in the heart and serum; reconstitution of the intestinal flora imbalance was also found in 5/6 Nx mice treated with YHJF. Spearman’s correlation and redundancy analyses showed that changes in the intestinal flora of 5/6 Nx mice were related to clinical phenotype and serum inflammatory levels. Conclusions: Treatment with YHJF effectively protected the heart function of 5/6 Nx mice; this effect was attributed to inhibition of NLRP3 inflammasome activation and regulation of intestinal microbial composition and derived metabolites. YHJF has potential for improving intestinal flora imbalance and gut-derived toxin accumulation in patients with CKD, thereby preventing cardiovascular complications.

Sirtuins, as regulators of metabolism and energy, have been found to play an important role in health and disease. Sirt1, the most widely studied member of the sirtuin family, can ameliorate oxidative stress, immune inflammation, autophagy, and mitochondrial homeostasis by deacetylating regulatory histone and nonhistone proteins. Notably, sirt1 has gradually gained attention in kidney disease research. Therefore, an evaluation of the overall distribution of publications concerning sirt1 based on bibliometric analysis methods to understand the thematic evolution and emerging research trends is necessary to discover topics with potential implications for kidney disease research. We conducted a bibliometric analysis of publications derived from the Web of Science Core Collection and found that publications concerning sirt1 have grown dramatically over the past 2 decades, especially in the past 5 years. Among these, the proportion of publications regarding kidney diseases have increased annually. China and the United States are major contributors to the study of sirt1, and Japanese researchers have made important contributions to the study of sirt1 in kidney disease. Obesity, and Alzheimer’s disease are hotspots diseases for the study of sirt1, while diabetic nephropathy is regarded as a research hotspot in the study of sirt1 in kidney disease. NAD+, oxidative stress, and p53 are the focus of the sirt1 research field. Autophagy and NLRP3 inflammasome are emerging research trends have gradually attracted the interest of scholars in sirt1, as well as in kidney disease. Notably, we also identified several potential research topics that may link sirt1 and kidney disease, which require further study, including immune function, metabolic reprogramming, and fecal microbiota.

Background: Podocyte injury has a direct causal relationship with proteinuria and glomerulosclerosis and, on a chronic level, can lead to irreversible disease progression. Podocyte injury plays a critically decisive role in the development of proteinuric kidney disease. In recent years, the research on podocyte injury has developed rapidly all over the world. However, no report has summarized the field of podocyte injury as a whole to date. Using bibliometric analysis, this study aimed to evaluate the current state of worldwide podocyte injury research in the last 30 years and identify important achievements, primary research fields, and emerging trends.Methods: Publications related to podocyte injury were retrieved from Web of Science Core Collection. HistCite, VOSviewer, CiteSpace, and the Bibliometrix Package were used for bibliometric analysis and visualization, including the analysis of the overall distribution of annual outputs, leading countries, active institutions and authors, core journals, co-cited references, and keywords. Total global citation score and total local citation score were used to assess the quality and impact of publications.Results: A total of 2,669 publications related to podocyte injury were identified. Publications related to podocyte injury tended to increase continuously. A total of 10,328 authors from 2,171 institutions in 69 countries published studies related to podocyte injury. China (39.46%) was the most prolific country, and the number of citations of studies in the United States (cited 36,896 times) ranked first. Moin A Saleem, John Cijiang He, and Zhihong Liu were the top three contributing authors, and Journal of the American Society of Nephrology and Kidney International were the most popular journals in the field. “Diabetic nephropathy” is the primary focus area of podocyte injury research, and “autophagy,” “microRNA,” and “inflammation” were the top keywords of emerging research hotspots, and traditional Chinese medicine monomer may be a neglected research gap.Conclusion: Our research found that global publications on podocyte injury have increased dramatically. Diabetic nephropathy is the main research field of podocyte injury, whereas autophagy, microRNA, and inflammation are the top topics getting current attention from scholars and which may become the next focus in podocyte injury research.

Facial palsy would lead to a series of physical and mental problems, as facial function plays an important role in various aspects of daily life. However, the current strategies for evaluating facial function relied heavily on raters and the results varied from the experience of raters. Thus, an objective and accurate facial evaluation system is always claimed. In this study, a customized automatical facial evaluation system (AFES) was proposed, which might have the potential to be employed as an adjunctive and efficient assessing method in clinic. In order to investigate the feasibility of AFES, ninety-two participants with facial palsy were recruited and received scale-based subjective manual evaluation (including mHBGS and mSFGS) and objective automatical evaluation of AFES (including aHBGS, aSFGS and indicators of facial regional features) at enrollment and after two weeks. The correlations between the results of the two methods were analyzed and the participants were stratified according to the severity of facial function for further analyses. Strong positive correlations between manual and automatical HBGS and SFGS were observed and higher correlations were reported in the participants with normal-mild and moderate facial palsy. Significant improvements in clinical scales and indicator of eye synkinesis were found in forty-two participants in two weeks. Furthermore, some of the indicators were correlated with scale scores (I4, I7) and one of them presented a significant change between the baseline evaluation and follow-up evaluation (I7). According to the results, AFES could be considered as a viable method to perform objective and reliable evaluation for patients with facial palsy and provide clarified results for prognosis.

Methyl gallate (MG) is a polyphenolic compound widely found in natural plants. MG has been shown to have a variety of biological functions, including anti-tumor, anti-inflammatory, anti-oxidant, neuroprotective, hepatoprotective and anti-microbial activities, and has broad research and development prospects. A total of 88 articles related to MG were searched using the PubMed, Science Direct, and Google Scholar databases, systematically investigating the pharmacological activity and molecular mechanisms of MG. There were no restrictions on the publication years, and the last search was conducted on June 5, 2023. MG can exert pharmacological effects through multiple pathways and targets, such as PI3K/Akt, ERK1/2, Caspase, AMPK/NF-κB, Wnt/β-catenin, TLR4/NF-κB, MAPK, p53, NLRP3, ROS, EMT. According to the literature, MG has the potential to be a prospective adjuvant for anticancer therapy and deserves further study.

Methyl gallate (MG), a polyphenolic compound found in plants, is widely used in traditional Chinese medicine. MG is known to alleviate several cancer symptoms. However, most studies that have reported the antitumor effects of MG have done so at the cellular level, and the inhibitory effect and therapeutic mechanism of MG in hepatocellular carcinoma (HCC) have not been extensively explored in vivo. We aimed to understand the therapeutic mechanism of MG in HCC in vitro and in vivo. MTT and colony formation assays were used to determine the impact of MG on the proliferation of a human HCC cell line, BEL-7402; wound healing and transwell assays were used to quantify the migration and invasion of HCC cells. Western blotting was used to quantify the expression of the AMPK/NF-κB signaling pathway proteins. In vivo tumor growth was measured in a xenograft tumor nude mouse model treated with MG, and hematoxylin–eosin staining and immunohistochemistry (IHC) were used to visualize the histological changes in the tumor tissue. We found that MG showed anti-proliferative effects both in vitro and in vivo. MG downregulated the protein expression of AMPK, NF-κB, p-NF-κB, and vimentin and upregulated the expression of E-cadherin in a dose-dependent manner. Additionally, MG inhibited the migration and invasion of HCC cells by decreasing MMP9 and MMP2 expression and increasing TIMP-2 expression. These were consistent with the results of IHC in vivo. MG inhibited the proliferation, migration, and invasion of HCC cells. This effect potentially involves the regulation of the AMPK/NF-κB pathway, which in turn impacts epithelial-mesenchymal transition and MMP expression.

Podophyllum sinense (P. sinense) has been used as a traditional herbal medicine for ages due to its extensive pharmaceutical activities, including antiproliferative, anti-inflammatory, antiviral, insecticidal effects, etc. Nevertheless, the specific bioactive constituents responsible for its antiproliferative, anti-inflammatory, and antiviral activities remain elusive, owing to its complicated and diversified chemical components. In order to explore these specific bioactive components and their potential interaction targets, affinity ultrafiltration with multiple drug targets coupled with high performance liquid chromatography/mass spectrometry (UF–HPLC/MS) strategy was developed to rapidly screen out and identify bioactive compounds against four well-known drug targets that are correlated to the application of P. sinense as a traditional medicine, namely, Topo I, Topo II, COX-2, and ACE2. As a result, 7, 10, 6, and 7 phytochemicals were screened out as the potential Topo I, Topo II, COX-2, and ACE2 ligands, respectively. Further confirmation of these potential bioactive components with antiproliferative and COX-2 inhibitory assays in vitro was also implemented. Herein, diphyllin and podophyllotoxin with higher EF values demonstrated higher inhibitory rates against A549 and HT-29 cells as compared with those of 5-FU and etoposide. The IC50 values of diphyllin were calculated at 6.46 ± 1.79 and 30.73 ± 0.56 μM on A549 and HT-29 cells, respectively. Moreover, diphyllin exhibited good COX-2 inhibitory activity with the IC50 value at 1.29 ± 0.14 μM, whereas indomethacin was 1.22 ± 0.08 μM. In addition, those representative constituents with good affinity on Topo I, Topo II, COX-2, or ACE2, such as diphyllin, podophyllotoxin, and diphyllin O-glucoside, were further validated with molecular docking analysis. Above all, the integrated method of UF–HPLC/MS with multiple drug targets rapidly singled out multi-target bioactive components and partly elucidated their action mechanisms regarding its multiple pharmacological effects from P. sinense, which could provide valuable information about its further development for the new multi-target drug discovery from natural medicines.

Selaginella doederleinii Hieron. (S. doederleinii) is a traditional herb that is widely used in China to treat several ailments, but mainly cancer. Studies have been carried out to determine the phytochemicals ascribed to its pharmacological activity. However, both phytochemical and pharmacological profiles have not been fully explored as few compounds have been reported. This study evaluated the flavonoid content of the ethanol extract and its four fractions (petroleum ether, dichloromethane, ethyl acetate, and n-butanol) together with their antioxidant activity (DPPH and FRAP assays). Further, the antiproliferative activity was evaluated. Two new secondary metabolites (1 and 3) were isolated from S. doederleinii, which comprised of an apigenin skeleton with a phenyl attached at C-8 of ring A and an acetyl group. Additionally, other known metabolites 2 and 4–16 were isolated, whereby compounds 2, 4, 5, 8, 12, 15, and 16 were reported for the first time in this species. These compounds were evaluated for their antioxidative potentials by both DPPH and FRAP assays, and for their antiproliferative activities by the MTT assay on three human cancer cell lines: colon cancer (HT-29), cervical cancer (HeLa), and lung cancer (A549). Compound 7 exhibited the best activity on the three cancer cell lines (HT-29, HeLa, A549) by inhibiting the rate of growth of the cancer cells in a dose-dependent manner with IC50 values of 27.97, 35.47, and 20.71 µM, respectively. The structure–activity relationship of the pure compounds was highlighted in this study. Hence, the study enriched both the phytochemical and pharmacological profiles of S. doederleinii.

Carissa spinarum has been traditionally used for the treatment of various diseases due to its different pharmacological activities. However, the active compounds responsible for its potentially specific activities have rarely been explored. To this end, the ethyl acetate (EA) fraction was screened out and selected for further phytochemical isolation because of its promising activities in preliminary 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and COX-2 inhibition assays. As a result, 10 compounds (1−10), including a new one (5), were isolated, with eight of these being identified as phenolic compounds, as expected. Compound 9 possessed an IC50 value of 16.5 ± 1.2 µM, which was lower than that of positive control (vitamin C, 25.5 ± 0.3 µM) in the DPPH assay, and compounds 2, 6, 7 and 9 showed better total antioxidant capacity than vitamin C in the FRAP assay. Meanwhile, compounds 1−6 and 9 also had IC50 values of less than 1.0 µM, which was even better than the positive control indomethacin in the COX-2 inhibition assay. In this context, compounds 2 and 9 were further evaluated to exhibit clear hepatoprotective activities by improving the L02 cell viability and reducing ROS production using a H2O2-induced L02 cell injury model. This study provides initial evidence revealing the most potent phenolic compounds from the root bark of C. spinarum responsible for its antioxidant, anti-inflammatory and hepatoprotective activities.

Hagenia abyssinica (Bruce) J. F. Gmel. is a multipurpose dioecious tree that has been used to treat various ailments, for example, the flowers of H. abyssinica have been widely used as a tea to treat intestinal parasites by local residents and the roots of H. abyssinica could also be used for anticancer purposes. Antioxidant activity could be one of the most important pathways to suppress cancer and there is hardly any information available on the specific chemical components corresponding to the bioactivities of H. abyssinica to date. The present study intended to screen and evaluate the antioxidant and anti-proliferative properties of five different fractions from H. abyssinica along with their corresponding total flavonoid and phenolic contents and then further identify those compounds with the most potent antioxidant and anti-proliferative activities using high performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) and nuclear magnetic resonance (NMR). The total flavonoid and phenolic content assays showed that the ethyl acetate (EA) fraction of H. abyssinica had higher flavonoid and phenolic levels than the other four fractions. Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) superoxide radical scavenging abilities, total antioxidant capacity (TAC) assay with 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP) were measured to evaluate the antioxidant activities of the five fractions and some pure compounds isolated from the EA fraction, which displayed higher antioxidant properties than that of the other fractions. Caffeic acid from the EA fraction showed even stronger DPPH scavenging ability (IC50 7.858 ± 0.31 µg/mL) than that of Vc (IC50 8.27 ± 0.11 µg/mL) as the positive control. The anti-proliferative properties of four fractions and the ethanol extract were evaluated by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and the EA fraction exhibited higher anti-proliferative activities against three cancer cell lines than that of the other fractions. Additionally, the compounds with good antioxidant activity from the EA fraction of H. abyssinica were screened and identified using LC-MS and NMR and were also found to possess good anti-proliferative activity. In the MTT assay, the quercetin showed the strongest dose-dependent anti-proliferative activities to colon cancer cells (HT-29) and liver cancer cells (HepG2) among all of the compounds isolated. This study provided valuable information on the synergistic antioxidant and anti-proliferative properties of H. abyssinica.