SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment.

Objective: Diabetic retinopathy (DR) is a severe diabetic complication that leads to severe visual impairment or blindness. He-Ying-Qing-Re formula (HF), a traditional Chinese medicinal concoction, has been identified as an efficient therapy for DR with retinal vascular dysfunction for decades and has been experimentally reported to ameliorate retinal conditions in diabetic mice. This study endeavors to explore the therapeutic potential of HF with key ingredients in DR and its underlying novel mechanisms. Methods: Co-expression gene modules and hub genes were calculated by weighted gene co-expression network analysis (WGCNA) based on transcriptome sequencing data from high-glucose-treated adult retinal pigment epithelial cell line-19 (ARPE-19). The chromatographic fingerprint of HF was established by ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-Q-TOF-MS). The molecular affinity of the herbal compound was measured by molecular docking. Reactive oxygen species (ROS) was measured by a DCFDA/H2DCFDA assay. Apoptosis was detected using the TUNEL Assay Kit, while ELISA, Western blot, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used for detecting the cytokine, protein, and mRNA expressions, respectively. Results: Key compounds in HF were identified as luteolin, paeoniflorin, and nobiletin. For WGCNA, ME-salmon ("protein deacetylation") was negatively correlated with ME-purple ("oxidative impairment") in high-glucose-treated ARPE-19. Luteolin has a high affinity for SIRT1 and P53, as indicated by molecular docking. Luteolin has a hypoglycemic effect on type I diabetic mice. Moreover, HF and luteolin suppress oxidative stress production (ROS and MDA), inflammatory factor expression (IL-6, TNF-α, IL1-ß, and MCP-1), and apoptosis, as shown in the in vivo and in vitro experiments. Concurrently, treatment with HF and luteolin led to an upregulation of SIRT1 and a corresponding downregulation of P53. Conclusion: Using HF and its active compound luteolin as therapeutic agents offers a promising approach to diabetic retinopathy treatment. It primarily suppressed protein acetylation and oxidative stress via the SIRT1/P53 pathway in retinal pigment epithelial cells.

Effects and mechanisms of anti-diabetic dietary natural products: an updated review.

Diabetes is a global public health issue, characterized by an abnormal level of blood glucose. It can be classified into type 1, type 2, gestational, and other rare diabetes. Recent studies have reported that many dietary natural products exhibit anti-diabetic activity. In this narrative review, the effects and underlying mechanisms of dietary natural products on diabetes are summarized based on the results from epidemiological, experimental, and clinical studies. Some fruits (e.g., grape, blueberry, and cherry), vegetables (e.g., bitter melon and Lycium barbarum leaves), grains (e.g., oat, rye, and brown rice), legumes (e.g., soybean and black bean), spices (e.g., cinnamon and turmeric) and medicinal herbs (e.g., Aloe vera leaf and Nigella sativa), and vitamin C and carotenoids could play important roles in the prevention and management of diabetes. Their underlying mechanisms include exerting antioxidant, anti-inflammatory, and anti-glycation effects, inhibiting carbohydrate-hydrolyzing enzymes, enhancing insulin action, alleviating insulin resistance, modulating the gut microbiota, and so on. This review can provide people with a comprehensive knowledge of anti-diabetic dietary natural products, and support their further development into functional food to prevent and manage diabetes.

Efficacy and safety of herbal medicines intervention for cachexia associated with cancer: A systematic review and meta-analysis.

As a worldwide public health issue, cancer-induced cachexia can result in decreasing physical function and survival rate. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise and nutritional intervention, are far from satisfactory. Herbal medicines (HMs), especially Traditional Chinese Medicine (TCM), are reported to effectively treat cachexia for centuries. The inclusion criteria of all participants in this study pointed to the diagnosis of cachexia, the trial group used herbal medicine (HM) in complementary and alternative medicine, etc. Twelve databases, including EMbase, PubMed, Web of science, Cochrane CENTRAL, CINAHL, CINAHLPlus, PsycINFO, AMED, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Chongqing VIP (CQVIP) were retrieved from inception to March 28, 2022. We conducted the meta-analysis utilizing RevMan 5.3. A trial sequential analysis (TSA) was conducted to assess the adequacy of the sample size for the outcomes. We have registered the protocol and the registration number was CRD42022336446. A total of 66 studies were included, containing 3654 patients diagnosed with cancer cachexia, of which 1833 patients were assigned to the trial group and 1821 patients were treated in the control group. Outcomes cover the primary indicator KPS (RR = 1.84, 95%CI = [1.61, 2.09], p < 0.00001), and other outcomes including adverse events rate (RR = 0.37, 95%CI = [0.23, 0.58], p < 0.0001), albumin (MD = 2.14, 95%CI = [1.56, 2.71], p < 0.00001), haemoglobin (MD = 4.88, 95%CI = [3.26, 6.50], p < 0.00001), TCM syndrome effect (MD = 1.47, 95%CI = [1.31, 1.65], p < 0.00001), effect of weight (RR = 1.62, 95%CI = [1.34, 1.95], p < 0.00001), effect of appetite (RR = 1.23, 95%CI = [1.13, 1.34], p < 0.00001), FAACT (RR = 7.81, 95%CI = [6.12, 9.50], p < 0.00001), PG-SGA (MD = -2.16, 95%CI = [-2.65, -1.67], p < 0.00001) and QOL (MD = 5.76, 95%CI = [4.04, 7.48], p < 0.00001), suggesting that HMs or HMs combined with conventional treatment have an ameliorating effect on cachexia in each respect. Subgroup analysis showed that the five HMs with the best effect on improving KPS and their optimal doses were Coicis Semen (Yiyiren) in 10 g group, Citri Reticulatae Pericarpium (Chenpi) in 15 g group, Dioscoreae Rhizoma (Shanyao) in 10 g group, Ophiopogonis Radix (Maidong) in 10 g group and Ginseng Radix Et Rhizoma (Renshen) in 20 g group. In addition, there were HM combinations of levels 2-6. Egger's test showed publication bias for five outcomes. HMs have a significant effect on improving cancer cachexia on FAACT, TCM syndrome, KPS, QOL, appetite, nutritional status (evaluated by PG-SGA scale), weight, levels of albumin and haemoglobin. And the Adverse events rate is less than that of Western Medicine. The herbs with the best curative effect and their optimal dose were Dioscoreae R. (10 g), Citri R.P. (15 g), Coicis S. (10 g), Ophiopogonis R. (10 g) and Ginseng R.E.R. (20 g). Due to the quality of included studies is not high, further high-quality studies are needed to firmly establish the clinical efficacy of HM.

Panax notoginseng-microbiota interactions: From plant cultivation to medicinal application.

BACKGROUND: Microbiomes and their host plants are closely linked with each other; for example, the microbiome affects plant growth, fitness, nutrient uptake, stress tolerance and pathogen resistance, whereas the host plant supports the photosynthetically carbon-rich nutrition of the microbiome. The importance of the microbiome in plant‒soil ecosystems is unquestioned and has expanded to influence the medicinal application of some herbal plants via the gut microbiota. PURPOSE: Herbal plant-microbiome interactions may provide novel knowledge to enhance the robustness of herbal plant crop performance and medicinal applications, which requires a systematic review and preceding discussion. STUDY DESIGN AND METHODS: The interactions between Panax notoginseng and microorganisms (from soil to host) were reviewed from the literature. The terms "Panax notoginseng" and "microbiota" were used in combination with the keywords "microbiota/microbes", "bacteria/bacterium" or "fungi/fungus" or "endophyte", as well as our targeted bioactive phytochemicals, including saponins and ginsenosides. RESULT: Our study focuses on the famous medicinal herb Panax notoginseng F. H. Chen and proposes that the microbiota is a crucial participant not only in the cultivation of this herbal plant but also in its medicinal application. We also summarize and discuss how these plant‒microbe co-associations shape the assembly of plant-related microbiomes and produce bioactive phytochemicals, as well as influence beneficial herbal traits, such as herbal plant health and pharmacology. In addition, we also highlight future directions. CONCLUSION: The rhizosphere and endophytic microbiome of Panax notoginseng are indirectly or directly involved in plant health, biomass production, and the synthesis/biotransformation of plant secondary metabolites. Harnessing the microbiome to improve the quality of traditional Chinese medicine and improve the value of medicinal plants for human health is highly promising.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .

Renal herb formula protects against hyperuricemic nephropathy by inhibiting apoptosis and inflammation.

BACKGROUND: Hyperuricemic nephropathy may be induced by the elevation and accumulation of uric acid in kidney after hyperuricemia, which leads to kidney residential cells apoptosis and inflammation. Renal herb formula (RHF) is a self-designed formula based on traditional Chinese medicine theory and clinical practice in kidney disease treatment. In the literature available currently, there is not yet research article reporting the reno-protective effect of RHF against hyperuricemic nephropathy. PURPOSE: This study was performed to analyze the bioactive compound profiles of RHF, evaluate its protective effects against hyperuricemic nephropathy, and investigate the mechanisms of actions regarding apoptosis and inflammation. METHODS: Ultra-performance liquid chromatography with a diode-array detector was applied to establish fingerprint and chemical composition of RHF. Potassium oxonate was used to induce hyperuricemic nephropathy in mice, and uric acid was used to stimulate apoptosis and inflammatory response in HK-2 cells, while the mice and cells were treated with RHF to explore its reno-protective effects and mechanisms. RESULTS: It was found that chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A-C may be the characteristic components of RHF. RHF treatment could improve kidney functions in mice with hyperuricemic nephropathies, such as decreasing urine protein, uric acid, and creatinine and serum uric acid, creatinine, and urea nitrogen. Histopathological observations showed that RHF treatment ameliorated kidney glomerular hypotrophy, tubular damage, and inflammatory infiltration. Mechanism studies revealed that RHF inhibited kidney residential cell apoptosis and inflammatory response by targeting the p53-associated intrinsic apoptosis pathway and NF-κB-mediated inflammatory pathway. CONCLUSION: Taken together, it could be concluded that RHF exerted reno-protective effects against hyperuricemic nephropathy through reducing apoptosis and inflammation. RHF and the bioactive compounds chlorogenic acid analogs as promising candidates may be developed into novel and effective drugs for hyperuricemic nephropathy treatment and management.

Deciphering suppressive effects of Lianhua Qingwen Capsule on COVID-19 and synergistic effects of its major botanical drug pairs.

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, ß-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis.

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Pharmacokinetic characteristics of emodin in polygoni Multiflori Radix Praeparata.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo. AIM OF THE STUDY: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. MATERIALS AND METHODS: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-ß-D-glycoside (EMG), physcion-1-O-ß-D-glycoside (PHG) and chrysophanol-8-O-ß-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. RESULTS: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), Tmax (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. CONCLUSION: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

Effects and mechanisms of tea on obesity.

Obesity has become a global health concern. It increases the risk of several diseases, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, and certain cancers, which threatens human health and increases social economic burden. As one of the most consumed beverages, tea contains various phytochemicals with potent bioactive properties and health-promoting effects, such as antioxidant, immune-regulation, cardiovascular protection and anticancer. Tea and its components are also considered as potential candidates for anti-obesity. Epidemiological studies indicate that regular consumption of tea is beneficial for reducing body fat. In addition, the experimental studies demonstrate that the potential anti-obesity mechanisms of tea are mainly involved in increasing energy expenditure and lipid catabolism, decreasing nutrient digestion and absorption as well as lipid synthesis, and regulating adipocytes, neuroendocrine system and gut microbiota. Moreover, most of clinical studies illustrate that the intake of green tea could reduce body weight and alleviate the obesity. In this review, we focus on the effect of tea and its components on obesity from epidemiological, experimental, and clinical studies, and discuss their potential mechanisms.

Potential Focal Adhesion Kinase Inhibitors in Management of Cancer: Therapeutic Opportunities from Herbal Medicine.

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and studies have revealed its biological behavior in tumor cell proliferation, migration, and adhesion. Herein we provide an overview of the complex biology of the FAK family members and their context-dependent nature. Next, with a focus on cancer, we highlight the activities of FAK signaling in different types of cancer and how knowledge of them is being used for screening natural compounds used in herbal medicine to fight tumor development.

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers.

Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.

Quality control, preparation process optimizing and anti-inflammatory effects of Premna Puberula Pamp. Pectin.

Background: Premna Puberula Pamp. Pectin (PP) was a Wudang functional food in China. It has the effect of dispelling fire, clearing heat and detoxification in folk medicine. However, little studies have been reported for their preparation, quality control, effects and toxicity. Methods: The P. Puberula leaves were collected from different pharms and seasons. The compounds in PP were identified using UPLC-Q-TOF-MS/MS. UV-VIS spectrophotometry with phenol-sulfuric acid and sodium nitrite aluminum nitrate were conducted for analyzing the water-soluble sugars and total flavonoids, respectively. L9(34) orthogonal experimental method was used to optimize the preparation process of PP. For the pharmacological effects of PP, the swelling right hind paw of ICR mice was modeled using subcutaneous injection of carrageenan gum solution, and the local tissue inflammatory reactions of the model mice were investigated using vernier calipers and HE staining. The serum inflammatory factor expression was detected using ELISA. The acute toxicity experiments were carried out for safety assessment of PP in ICR mice. Results: Fifty-three compounds were initially identified in PP among which flavonoids were dominant (19 out of 53). The average values of water-soluble sugar content and total flavonoid content of PP were 13.366 and 4.970 mg/g, respectively. The best preparation process of PP was powder-liquid ratio 1: 20, temperature 90 °C, and stirring time 3 min. Data showed that PP reduced paw edema and decrease the serum level of IL-6, TNF-α and IL-1ß in the model mice. There was no toxic effect of PP on mice at a total dose of 6000 mg/kg/24h. Conclusion: In summary, by optimizing the preparation process, PP with stable quality can be obtained. PP has anti-inflammatory effects without toxicity.

Bioactivities and Mechanism of Actions of Dendrobium officinale: A Comprehensive Review.

Dendrobium officinale has a long history of being consumed as a functional food and medicinal herb for preventing and managing diseases. The phytochemical studies revealed that Dendrobium officinale contained abundant bioactive compounds, such as bibenzyls, polysaccharides, flavonoids, and alkaloids. The experimental studies showed that Dendrobium officinale and its bioactive compounds exerted multiple biological properties like antioxidant, anti-inflammatory, and immune-regulatory activities and showed various health benefits like anticancer, antidiabetes, cardiovascular protective, gastrointestinal modulatory, hepatoprotective, lung protective, and neuroprotective effects. In this review, we summarize the phytochemical studies, bioactivities, and the mechanism of actions of Dendrobium officinale, and the safety and current challenges are also discussed, which might provide new perspectives for its development of drug and functional food as well as clinical applications.

Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses.

The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped viruses. The viral inhibitory activities of the SSP were evaluated by using pseudotyped SARS-CoV-1 and 2, HIV-1ADA and HXB2 , and H5N1. SSP effectively inhibited viral entry and with EC50 values ranging from 3.6 to 5.1 µg/ml. Pre-treatment of pseudovirus or target cells with SSP showed consistent inhibitory activities with the respective EC50 value of 2.3 or 2.1 µg/ml. SSP blocked both SARS-CoV-2 spike glycoprotein and the host ACE2 receptor. In vivo studies indicated that there was no abnormal toxicity and behavior in long-term SSP treatment. Based on these findings, we concluded that SSP has the potential to be developed as a drug candidate for preventing and treating COVID-19 and other emerging enveloped viruses.

Medicinal Plants for the Treatment of Gastrointestinal Cancers From the Metabolomics Perspective.

Gastrointestinal cancer (GIC), primarily including colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, and esophageal cancer, is one of the most common causes of cancer-related deaths with increasing prevalence and poor prognosis. Medicinal plants have been shown to be a great resource for the treatment of GIC. Due to their complex manifestations of multi-component and multi-target, the underlying mechanisms how they function against GIC remain to be completely deciphered. Cell metabolism is of primary importance in the initialization and development of GIC, which is reported to be a potential target. As an essential supplement to the newest "omics" sciences, metabolomics focuses on the systematic study of the small exogenous and endogenous metabolites involved in extensive biochemical metabolic pathways of living system. In good agreement with the systemic perspective of medicinal plants, metabolomics offers a new insight into the efficacy assessment and action mechanism investigation of medicinal plants as adjuvant therapeutics for GIC therapy. In this review, the metabolomics investigations on metabolism-targeting therapies for GIC in the recent 10 years were systematically reviewed from five aspects of carbohydrate, lipid, amino acid, and nucleotide metabolisms, as well as other altered metabolisms (microbial metabolism, inflammation, and oxidation), with particular attention to the potential of active compounds, extracts, and formulae from medicinal plants. Meanwhile, the current perspectives and future challenges of metabolism-targeting therapies of medicinal plants for GIC were also discussed. In conclusion, the understanding of the action mechanisms of medicinal plants in GIC from the metabolomics perspective will contribute to the clinical application of potential candidates from the resourceful medicinal plants as novel and efficient adjuvant therapeutics for GIC therapy.

The Role and Mechanisms of Selenium Supplementation on Fatty Liver-Associated Disorder.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease without effective therapy. Selenium, as an essential trace element for humans, is notable for its antioxidant properties. The previous study shows that selenium levels in NAFLD patients are lower than normal ones. Selenium supplementation can effectively alleviate metabolic disorders by relieving anti-oxidative stress and anti-inflammatory regulation. However, the correlation between selenium and NAFLD has not been fully clarified. Herein, we review the current studies on selenium in regulating the different stages of NAFLD and summarize relevant clinical trials to highlight the potential roles of selenium in NAFLD treatment.

Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications.

Elderberry (Sambucus nigra L.) is rich in many bioactive compounds and exhibits diverse health functions, of which an understanding can be helpful for its better utilization in the food industry. This review mainly summarizes recent studies about the bioactive compounds and health functions of elderberry, highlighting the potential mechanism of action. In addition, the applications of elderberry in foods are also discussed. Elderberry contains diversely bioactive ingredients, such as (poly)phenolic compounds and terpenoid compounds. Recent studies report that some food processing methods can affect the content of bioactive compounds in elderberry. Additionally, elderberry exhibits various health functions in vitro and in vivo, including antioxidant, anti-inflammatory, anticancer, anti-influenza, antimicrobial, antidiabetic, cardiovascular protective, and neuroprotective activities, and their potential molecular mechanisms are associated with regulating some key signaling pathways and molecular targets. Up to now, there have been limited clinical trials supporting the health benefits of elderberry. Overall, elderberry is a promising dietary source of bioactive ingredients and has the potential to be developed into functional foods or nutraceuticals for preventing and treating certain chronic diseases.