Visible light (VL) accounts for approximately 50% of the solar radiation reaching Earth’s surface and has emerged as a major contributor to skin photoaging and pigmentation disorders, particularly in individuals with darker Fitzpatrick skin phototypes. Increasing evidence suggests that VL exposure induces oxidative stress, inflammation, and melanogenesis by generating reactive oxygen species. In this study, we investigated the protective effects of a topical antioxidant formulation (AOX Mix) containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol against VL exposure in ex vivo skin biopsies from donors with Fitzpatrick skin phototypes IV–V. To preserve physiological tissue tension and closely replicate in vivo skin responses, human skin explants were maintained using the TenSkin™ culture system. Samples were pretreated with AOX Mix for 30 min, then exposed to VL for 8 h, and collected on Days 2 and 7 for histological and molecular analyses. Our results demonstrated that prolonged exposure to VL disrupted redox homeostasis and induced structural alterations in skin explants, accompanied by increased markers of oxidative stress and pigmentation. In contrast, pre-treatment with AOX Mix significantly attenuated these effects, preserving tissue architecture and reducing molecular indicators of photodamage. In addition, we observed the co-localization of 4-hydroxynonenal and collagen type I, suggesting that oxidative post-translational modification of collagen may contribute to its loss. These findings suggest that antioxidant-based interventions, such as AOX Mix, may be a promising strategy for protecting dark skin against VL exposure.

Obesity and type 2 diabetes are associated with alterations in gut microbial composition and host nutrient metabolism, both of which can modify the bioconversion of dietary compounds. Consequently, identical dietary substrates may generate distinct metabolite profiles, leading to different physiological responses. Emerging evidence suggests that many biological effects of dietary compounds are mediated, in part, by metabolites generated through host and microbial bioconversion. These metabolites regulate key pathways involved in oxidative stress, inflammatory signaling, glucose metabolism, and gut barrier integrity. Altered bioconversion efficiency observed in obesity and type 2 diabetes may therefore influence metabolic outcomes by altering the quantity and composition of bioactive metabolites. This review summarizes current evidence on the metabolic effects of bioconversion-derived metabolites generated from dietary components and discusses their underlying molecular mechanisms in obesity and type 2 diabetes. By focusing on metabolites generated through dietary bioconversion rather than dietary substrates alone, this review proposes a metabolite-centered framework for understanding variability in dietary responses and identifying metabolically relevant targets for future nutritional interventions.

Background/Objectives: Skeletal muscle–derived myokines have emerged as pivotal mediators of the muscle–brain axis, linking peripheral metabolic regulation with central nervous system function. These molecules may influence skeletal muscle maintenance, neuroplasticity, neuroinflammation, and cognitive performance, and their dysregulation is increasingly associated with metabolic and cognitive impairment. In obesity (OB) and type 2 diabetes mellitus (T2DM), dysregulated myokine profiles characterized by reduced levels of irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B (CTSB) have been reported and may contribute to the development of both sarcopenia and cognitive impairment. This review aims to summarize current evidence on myokine alterations in OB and T2DM and to evaluate how exercise- and nutrition-based interventions may modulate the muscle–brain axis to support metabolic and cognitive health. Methods: This narrative review synthesizes experimental, clinical, and translational studies examining (1) alterations in circulating myokines in OB and T2DM, (2) associations between myokines, skeletal muscle function, and neurocognitive outcomes, and (3) the modulatory effects of exercise and specific nutrients on myokine-mediated muscle–brain communication. Results: Available evidence indicates that OB and T2DM are frequently accompanied by reduced circulating levels of beneficial myokines such as irisin, BDNF, and CTSB, which may impair skeletal muscle integrity and contribute to cognitive decline. Restoring favorable myokine signaling through physical activity appears to enhance skeletal muscle maintenance, neuroplasticity, and metabolic homeostasis. Emerging data further suggest that selected nutrients can mimic or potentiate some exercise-induced myokine responses, thereby supporting both muscle and brain function. Collectively, these findings imply that combined exercise and nutrition strategies may exert synergistic or additive effects by reinforcing inter-organ communication along the muscle–brain axis. Conclusions: This review outlines current evidence on myokine alterations observed in OB and T2DM and discusses how exercise- and nutrition-based approaches may modulate the muscle–brain axis to mitigate metabolic dysfunction and preserve cognitive health. Targeting beneficial myokine pathways through tailored lifestyle interventions represents a promising avenue to support both skeletal muscle and neurocognitive function in individuals with metabolic disease.

Skeletal muscle atrophy is one of the serious complications of diabetes, which increases the risk of frailty, falls, and mortality. However, interventions for muscle atrophy are limited, and research is needed regarding the treatment of muscle wasting. Recently, the bioconversion of natural products by lactic acid bacteria has been highlighted as a possibility to improve the bioavailability of active ingredients. This process also produces metabolites, which are key signaling mediators for a variety of physiological functions. This study investigated the effect of bioconverted guava leaf (Psidium guajava L., GL) by Lactobacillus plantarum on hyperglycemia-induced skeletal muscle atrophy in type 2 diabetes mellites (T2DM) mice. Diabetes was induced by a high-fat diet with a two-time streptozotocin (STZ) injection (60 mg/kg BW) in male C57BL/6J mice. After diabetes was induced (a fasting blood glucose level (FBG) ≥ 300 mg/dL), the mice were administered with GL (100 mg/kg/day) or bioconverted GL (FGL) (50 mg/kg/day) by oral gavage for 14 weeks. FGL contains different substances such as hydroxyl-isocaproic acid and hydroxyl-isovaleric acid compared to GLE itself, which have potential to prevent muscle degradation in T2DM mice. GL and FGL supplementation reduced the FBG level in T2DM mice. In addition, GL and FGL supplementation enhanced muscle strength, the skeletal muscle cross-sectional area, and ameliorated ubiquitin-proteasome system (UPS)-related pathways in T2DM mice. On the other hand, GLE supplementation ameliorated glucose tolerance demonstrated by oral glucose tolerance test and enhanced insulin signaling pathway. In addition, only FGL supplementation attenuated skeletal muscle inflammation and apoptosis with an improved mammalian target of the rapamycin (mTOR)-autophagy-related pathway. Although administered at a half dose of GLE, FGL demonstrated greater efficacy in regulating the expression of these molecular markers. The result suggests that even GL itself has anti-diabetic effects, and the functionality would be enhanced by the bioconversion of GL with L. Plantarum, which has an additive or/and a synergistic effect. Taken together, FGL could be used as a potential nutraceutical to attenuate muscle degradation by the inhibition of inflammation, the UPS, and the apoptosis pathway.

Background/Objectives: Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease, a condition associated with high mortality risks. Recently, supplementation with probiotics and postbiotics has been attracting attention. Especially, metabolites of natural products bioconverted by beneficial bacteria have emerged as a novel therapeutic intervention for metabolic diseases, including diabetes, due to the enhanced bioavailability of their metabolites. This study investigated the alleviating effects of metabolites derived from guava leaf extract bioconverted by Limosilactobacillus fermentum (GBL) on renal inflammation in type 2 diabetic mice. Methods: For this purpose, diabetes was induced in male C57BL/6J mice by a high-fat diet and streptozotocin injection (80 mg/kg BW) twice. Subsequently, mice with fasting blood glucose levels higher than 300 mg/dL were administered metabolites of L. fermentum (LF) (50 mg/kg BW/day) or guava leaf extract bioconverted by L. fermentum (GBL) (50 mg/kg BW/day) by oral gavage for 15 weeks. Results: GBL demonstrated potential in alleviating hyperglycemia-induced DN in diabetic mice. It markedly improved hyperglycemia, glucose tolerance, and morphological alterations, which might stem from activation of key regulators of energy metabolism. GBL uniquely reduced advanced glycation end products (AGEs) and suppressed nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-driven inflammatory pathways, which significantly alleviated oxidative stress and apoptosis. Conclusions: This highlights the distinct therapeutic efficacy of GBL in addressing DN, primarily through its effects on renal inflammation. Taken together, GBL can be used as a promising nutraceutical to mitigate hyperglycemia and its associated renal inflammation, thereby alleviating the progression of DN.

Ozone-induced inflammation has been linked to the development of skin ailments including atopic dermatitis, acne vulgaris, eczema and psoriasis, mainly through a redox-inflammatory pathway. While ozone cannot penetrate the cutaneous layers, it is able to damage the skin through oxinflammatory reactions in the epidermis that lead to the generation of lipid-peroxides, aldehydes, and H2O2. When the production of these bioactive oxidative molecules overwhelms the cutaneous redox defenses, cutaneous damage incurs. Antimicrobial peptides (AMPs) are effector molecules that regulate a variety of cutaneous immune responses. Increased AMPs levels have also been detected in active lesions of inflammatory skin diseases. Our previous research has shown that exposure to either ozone induced the expression of cutaneous AMPs (LL-37, β-defensin 2, and β-defensin 3) levels in ex vivo skin explants, corroborating the hypothesis that ozone exposure might worsen inflammatory skin conditions via AMPs de-regulation. In the present work, to further assess the cutaneous AMPs responses in a more physiological setting, skin models cultured under physiological tension (TenBio) were expose to ozone. As a proof of concept, cutaneous models were pre-treated with a variety of redox inhibitors (catalase, deferoxamine (DFO) and VAS2870 (VAS)) before ozone exposure to better understand the involvement of a redox signaling. Our data demonstrates that even in the most realistic cutaneous ex vivo model, ozone induces LL-37, hBD2, and hBD3 protein levels through a redox mechanism. This study lays the basis to uncover the mechanisms of ozone dysregulation of cutaneous AMPs, a fundamental step to understanding the development/worsening of pollution-linked inflammatory skin conditions.

OBJECTIVES:This study evaluated the effects of protein-enriched oral nutritional supplementation (ONS) consumption for 12 weeks on muscle mass, muscular strength, and function in middle-aged and elderly women. DESIGN:A single-center, double-blind, randomized controlled trial PARTICIPANTS: This study was conducted with 70 healthy female participants aged 50-80. INTERVENTION AND MEASUREMENTS:Participants were instructed to incorporate two daily packs of either the test ONS (Nucare Active, Daesang Wellife Corp., Seoul, Republic of Korea; 200 kcal/pack, 23 g carbohydrate, 6 g fat, and 15 g protein including branched chain amino acids or placebo ONS (200 kcal/pack, 33 g carbohydrate, 8 g fat, and 1 g protein) into their routine for 12 weeks while maintaining their regular lifestyle. The primary outcome was lean body mass (LBM), while secondary outcomes included muscular strength, physical performance ability, inflammatory markers, and body fat mass (FM). RESULTS:Sixty-four participants (33 in the test group, 31 in the placebo group; mean ± SD age, [test] 63.06 ± 5.51 years, [placebo] 63.29 ± 3.28 years, p = 0.839) completed the 12-week protocol. The test group exhibited a higher percentage change in LBM than the placebo group (0.26 % [95%CI: -0.27, 0.78] vs. -0.47 % [95%CI: -0.81, -0.13]; p = 0.020). The placebo group experienced a significant increase in FM (38.15 % [95%CI: 36.62, 39.69] to 38.67 % [95%CI: 37.14, 40.21]; p < 0.01). The difference in the changes in LBM/BMI and FM/BMI between the two groups was also visually distinct. There were no significant differences between the two groups in terms of muscular strength, physical performance ability, or inflammatory markers. CONCLUSIONS:Protein-enriched ONS helped maintain LBM and prevent FM gain in middle-aged and elderly females. This suggests its potential role in preventing frailty and musculoskeletal disorders associated with female aging.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is considered a serious risk to public health since its prevalence is rapidly increasing worldwide despite numerous therapeutics. Insulin resistance in T2DM contributes to chronic inflammation and other metabolic abnormalities that generate fat accumulation in the liver, eventually leading to the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Recently, the possibility that microbial-derived metabolites may alleviate MAFLD through enterohepatic circulation has emerged, but the underlying mechanism remains unclear. In this research, we utilized metabolites obtained from the fermentation of guava leaf extract, which is well-known for its antidiabetic activity, to investigate their effects and mechanisms on MAFLD. Methods: Diabetes was induced by a high-fat diet and streptozotocin injection (80 mg/kg body weight) twice in mice. Subsequently, mice whose fasting blood glucose levels were measured higher than 300 mg/dL were administered with metabolites of Limosilactobacillus fermentum (LF) (50 mg/kg/day) or guava leaf extract fermented by L. fermentum (GFL) (50 mg/kg/day) by gavage for 15 weeks. Results: GFL supplementation mitigated hyperglycemia and hepatic insulin resistance. Moreover, GFL regulated abnormal hepatic histological changes and lipid profiles in diabetic mice. Furthermore, GFL enhanced energy metabolism by activating the sirtuin1 (SIRT1)/proliferator-activated receptor γ coactivator 1α (PGC1α)/peroxisome proliferator-activated receptor (PPAR)-α pathway in diabetic mice. Meanwhile, GFL supplementation suppressed hepatic inflammation in diabetic mice. Conclusions: Taken together, the current study elucidated that GFL could be a potential therapeutic to ameliorate hyperglycemia and hepatic steatosis by improving SIRT1/PGC-1α/ PPAR-α-related energy metabolism in T2DM.

In this study, we investigated the protective effects of SM on skeletal muscle and brain damage by regulation of BDNF/PGC1α/irisin pathway via brain function related myokines in high-fat diet-induced OB mice. OB was induced by high-fat diet for 6 weeks. SM extract (SME) was administered with 200 mg/kg BW (LSM) and 500 mg/kg BW (HSM) by oral gavage every day for 12 weeks. Behavior tests such as grip strength, Y-maze, and passive avoidance test were conducted to analyze muscle and cognitive function. Histopathological changes in skeletal muscle and brain were examined by hematoxylin and eosin staining and the protein levels of biomarkers related to oxidative stress, inflammation, protein degradation, neuro-plasticity, and cell cycling were measured by western blot. SME regulated morphological changes (muscle cross-sectional area: 1.23%, 1.40%; density of neurons in hippocampus:1.74%, 1.73%) in T2DM mice. Importantly, SME supplementation significantly increased several muscle-derived myokines which might influence the expression of neuronal markers in OB mice (FGF21: 1.27%, 1.34%; PGC1α: 1.0%, 1.32%; IRISIN: 1.9%, 1.08%; BDNF: 1.35%, 1.23%). Accordingly, SME activated hippocampal neurotrophic factors including BDNF (1.0%, 1.2%) and its associated PGC1α/irisin pathway (PGC1α :1.1%, 1.1%; IRISIN:1.1%, 0.9%) significantly. This study demonstrated the possibliy that protective myokines increased by SME supplementation may contribute to neuro-protection in OB mice. Taken together, the current study suggests that SME can be used to prevent skeletal muscle and brain damage in OB by protecting against oxidative stress and inflammatin via modulation of the BDNF/PGC1α/irisin pathway in the therapeutic approach of obese patients.

Muscle atrophy is the waste or loss of muscle mass. Muscle atrophy is caused by physical inactivity, aging, or diseases such as diabetes, cancer, and heart failure. The number of patients suffering from musculoskeletal disorders is expected to increase in the future. However, intervention for muscle atrophy is limited, so research to treatment for muscle wasting is needed. This study hypothesized that guava leaf (Psidium guajava L., GL) would have ameliorative effects on muscle atrophy by regulation of protein degradation pathways in dexamethasone (DEX)-indued muscle atrophy mice model. Muscle atrophy was induced by DEX injection for 28 days in 7 weeks old male ICR mice. Then, low dose (LGL, 200 mg/kg) or high dose (HGL, 500 mg/kg) of GL extract (GLE) was supplemented by oral gavage for 21 days. Muscle strength, calf thickness, and body composition were analyzed. Histopathological changes in gastrocnemius muscle were examined using hematoxylin and eosin staining, and molecular pathways related to muscle degradation were analyzed by western blots. GLE treatment regardless of dose increased muscle strength in mice with muscle atrophy accompanied by attenuating autophagy related pathway in the DEX-induced muscle atrophy mice. Moreover, high dose of GLE treatment ameliorated ubiquitin proteasome system and apoptosis in the DEX-induced muscle atrophy mice. This study suggested that GLE could be helpful to improve muscle health and alleviate proteolysis by regulation of UPS, autophagy, and apoptosis, which are involved in muscle degradation. In conclusion, GLE would be a potential nutraceutical to prevent muscle atrophy.

The present study aimed to investigate the effect of 6-shogaol (6S) treatment on brain senescence. Mice were naturally aged until 25-month-old and treated with 10 mg/kg of 6S for a month. Behavioral tests were performed to measure locomotion and cognitive function. Neuronal damage, synaptic plasticity, neuroinflammation, neurogenesis and p75 neurotrophin receptor (p75NTR) expression were examined by immunohistochemistry or immunofluorescence. 6S treatment improved locomotion during open field test in the aged mice and spontaneous alternation in Y-maze. These data are in line with that 6S administration improved dopaminergic neuronal loss and dopamine signaling and attenuated hippocampal synaptic plasticity in the aged brain. Additionally, 6S treatment reduced striatal and hippocampal microgliosis and astrocytosis but promoted neurogenesis in subventricular zone. Furthermore, 6S treatment reversed the p75NTR expression in the senescent brain. The current findings suggest that 6S can be a functional food for successful aging through brain rejuvenation at the molecular level.

Reactive oxygen species (ROS) are highly bioactive molecules involved not only in tissue physiology but also in the development of different human conditions, including premature aging, cardiovascular pathologies, neurological and neurodegenerative disorders, inflammatory diseases, and cancer. Among the different human tumors, cutaneous melanoma, the most aggressive and lethal form of skin cancer, is undoubtedly one of the most well-known “ROS-driven tumor”, of which one of the main causes is represented by ultraviolet (UV) rays’ exposure. Although the role of excessive ROS production in melanoma development in pro-tumorigenic cell fate is now well established, little is known about its contribution to the progression of the melanoma metastatic process. Increasing evidence suggests a dual role of ROS in melanoma progression: excessive ROS production may enhance cellular growth and promote therapeutic resistance, but at the same time, it can also have cytotoxic effects on cancer cells, inducing their apoptosis. In this context, the aim of the present work was to focus on the relationship between cell redox state and the signaling pathways directly involved in the metastatic processes. In addition, oxidative or antioxidant therapeutic strategies for metastatic melanoma were also reviewed and discussed.

Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.

Tyrosine kinase has been implicated in viral replication and has become an antiviral drug target. Here, we chose two well-known receptor tyrosine kinase inhibitors, amuvatinib and imatinib, and evaluated their drug potencies against SARS-CoV-2.

Levodopa (L-dopa) and catechol-O-methyltransferase (COMT) inhibition are widely used therapeutics in Parkinson’s disease (PD). Despite their therapeutic effects, it was raised that nutrients involved in one-carbon metabolism can be deteriorated by PD therapies. The aim of this meta-analysis was to investigate the impact of L-dopa and COMT inhibitors on levels of homocysteine (Hcy), vitamin B12 and folate in patients with PD. A total of 35 case-control studies from 14 different countries were selected through PubMed, MEDLINE and Google Scholar and were meta-analyzed. In the L-dopa group, the Hcy level was higher compared to the PD without L-dopa group (SMD: 5.11 μmol/L, 95% CI: 3.56 to 6.66). Moreover, vitamin B12 and folate levels in the L-dopa group were lower compared to the healthy control (SMD: −62.67 pg/mL, 95% CI: −86.53 to −38.81; SMD: −0.89 ng/mL, 95% CI: −1.44 to −0.33, respectively). The COMT inhibitor group showed lower levels of Hcy (SMD: −3.78 μmol/L, 95% CI: −5.27 to −2.29) and vitamin B12 (SMD: −51.01 pg/mL, 95% CI: −91.45 to −10.57), but higher folate levels (SMD: 1.78 ng/mL, 95% CI: −0.59 to 4.15) compared to the L-dopa group. COMT inhibitors may ameliorate L-dopa-induced hyper-homocysteine and folate deficiency but exacerbate vitamin B12 deficiency.

ABSTRACT RAD51 is an important factor involved in the homologous recombination and repair of DNA breaks, which has also been implicated in various virus replication processes. We have previously reported that hepatitis C virus (HCV) exploits cellular RAD51 to promote viral propagation. Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also an RNA virus, we interrogated whether SARS-CoV-2 could coopt RAD51 for its propagation. Here, we showed that silencing of RAD51 impaired SARS-CoV-2 propagation. We further demonstrated that RAD51 colocalized with SARS-CoV-2 RNA in Vero E6 cells. Interestingly, RAD51 interacted with SARS-CoV-2 3CL protease. This suggests that RAD51 inhibitors may block SARS-CoV-2 propagation. Hence, we evaluated multiple RAD51 inhibitors as potential drug candidates for coronavirus disease 2019 (COVID-19). Among these, B02, 4 ' -diisothiocyanostilbene-2,2 ' -disulfonic acid (DIDS), IBR2, and RI(dl)-2 significantly decreased RNA, protein, and infectious virion levels of Wuhan and variants of SARS-CoV-2. Antiviral activity of DIDS was further confirmed in the Syrian hamster model. Molecular docking model showed that these chemicals interfered with RAD51 through dimerization interface. These data suggest that SARS-CoV-2 exploits host RAD51 to facilitate viral propagation, and hence, RAD51 inhibitor may serve as a putative novel therapeutic agent for the treatment of COVID-19. IMPORTANCE Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly affects respiratory tracts including the trachea and lungs. As inflammation and cytokine storm are major pathological features in a Syrian hamster for SARS-CoV-2 infection, reducing inflammatory responses or antiviral therapy is an effective strategy for treating SARS-CoV-2 infections. Herbal medicines and natural substances are applied worldwide due to their health-beneficial effects. Although chemical and pharmacological verifications have not been made for all substances, the pharmacological effects of many substances are being studied. In this study, Boswellia serrata, Commiphora myrrha, and propolis known to have anti-inflammatory and antimicrobial properties were selected as candidates for therapeutic herbal medicine targeting SARS-CoV-2. When this herbal mixture was treated to SARS-CoV-2 infected Vero E6 and Calu-3 cells, effective antiviral effects were demonstrated. Next, this herbal mixture was administered to SARS-CoV-2-infected Syrian hamsters, and histopathological lesions were significantly reduced. Viral spike protein and viral enzyme gene were also significantly less detected in immunohistochemistry and quantitative real-time PCR results, respectively. Thus, it can be concluded that a mixture of Boswellia serrata, Commiphora myrrha, and propolis as natural substances has the potential to reduce lesions of respiratory tracts upon SARS-CoV-2 infection.

African swine fever virus (ASFV), an extremely contagious virus with high mortality rates, causes severe hemorrhagic viral disease in both domestic and wild pigs. Fortunately, ASFV cannot be transmitted from pigs to humans. However, ongoing ASFV outbreaks could have severe economic consequences for global food security. Although ASFV was discovered several years ago, no vaccines or treatments are commercially available yet; therefore, the identification of new anti-ASFV drugs is urgently warranted. Using molecular docking and machine learning, we have previously identified pentagastrin, cangrelor, and fostamatinib as potential antiviral drugs against ASFV. Here, using machine learning combined with docking simulations, we identified natural products with a high affinity for AsfvPolX proteins. We selected five natural products (NPs) that are located close in chemical space to the six known natural flavonoids that possess anti-ASFV activity. Polygalic acid markedly reduced AsfvPolX polymerase activity in a dose-dependent manner. We propose an efficient protocol for identifying NPs as potential antiviral drugs by identifying chemical spaces containing high-affinity binders against ASFV in NP databases.

Type 2 diabetes mellitus (T2DM) is related with the incidence of sarcopenia and cognitive impairment that reduces quality of life in the elderly. Recent evidence has demonstrated that sarcopenia is associated with cognitive dysfunction, and muscle-derived endocrine factors might contribute to cognitive function by the skeletal muscle–brain endocrine loop. This study investigated the beneficial effects of Annona muricata (AM, graviola) on multi-organ energy metabolism with muscle–brain connectivity via brain function-related myokines in mice. Body composition, fasting blood glucose level, insulin, HbA1c%, histopathological changes, and the protein levels of insulin-signaling, energy metabolism, neuroprotection, inflammation, and protein-degradation pathways were measured. AM extract (AME) treatment selectively enhanced insulin signaling in the skeletal muscle and hippocampus of T2DM mice. Furthermore, AME treatment effectively increased muscle-derived fibroblast growth factor 21 (FGF21), cathepsin-B (CTSB), irisin, brain-derived neurotrophic factor (BDNF), and liver-derived FGF21 that contribute to whole-body energy homeostasis. In particular, AME increased the levels of circulating myokines (FGF21, BDNF, irisin, and CTSB), and these were accordance with the hippocampal neurotrophic factors (BDNF and CTSB) in T2DM mice. In conclusion, we suggest that AME would be a potential nutraceutical for improving the energy metabolism associated with muscle–brain connectivity via brain function-related myokines in T2DM.

Natural products and herbal medicine have been widely used in drug discovery for treating infectious diseases. Recent outbreak of COVID-19 requires various therapeutic strategies. Here, we used YSK-A, a mixture of three herbal components Boswellia serrata, Commiphora myrrha, and propolis, to evaluate potential antiviral activity against SARS-CoV-2. We showed that YSK-A inhibited SARS-CoV-2 propagation with an IC50 values of 12.5 µg/ml and 15.42 µg/ml in Vero E6 and Calu-3 cells, respectively. Using transcriptome analysis, we further demonstrated that YSK-A modulated various host gene expressions in Calu-3 cells. Among these, we selected 9 antiviral- or immune-related host genes for further study. By siRNA-mediated knockdown experiment, we verified that MUC5AC, LIF, CEACAM1, and GDF15 host genes were involved in antiviral activity of YSK-A. Therefore, silencing of these genes nullified YSK-A-mediated inhibition of SARS-CoV-2 propagation. These data indicate that YSK-A displays an anti-SARS-CoV-2 activity by targeting multiple antiviral genes. Although the exact antiviral mechanism of each constituent has not been verified yet, our data indicate that YSK-A has an immunomodulatory effect on SARS-CoV-2 and thus it may represent a novel natural product-derived therapeutic agent for treating COVID-19.