Asthma is a chronic inflammatory disease involving structural changes to the respiratory system and severe immune responses mediated by allergic cytokines and pro-inflammatory mediators. Agarum cribrosum (AC) is a kind of seaweed which contains a phlorotannin, trifuhalol A. To evaluate its anti-allergic inflammatory effect against asthma, an ovalbumin inhalation-induced mouse asthma model was used. Histologic observations proved that trifuhalol A is minimizing the lung and tracheal structure changes as well as the infiltration of eosinophils and mast cells against ovalbumin inhalation challenge. From the serum and bronchoalveolar lavage fluid, ovalbumin-specific IgE and Th2-specific cytokines, IL-4, -5, and -13, were reduced with trifuhalol A treatment. In addition, IL-1β, IL-6, and TNF-α concentrations in lung homogenate were also significantly reduced via trifuhalol A treatment. Taken together, trifuhalol A, isolated from AC, was able to protect lung and airways from Th2-specific cytokine release, and IgE mediated allergic inflammation as well as the attenuation of IL-1β, IL-6, and TNF-α in lung, which results in the suppression of eosinophils and the mast cells involved asthmatic pathology.

Non-alcoholic fatty liver disease (NAFLD, recently renamed as metabolic dysfunction-associated steatotic liver disease [MASLD]) has emerged as one of the most prevalent chronic liver diseases globally. The more severe progressive form of the disease is called nonalcoholic steatohepatitis (NASH, now termed metabolic dysfunction-associated steatohepatitis [MASH]). The rising prevalence of NASH is placing an increasing burden on global healthcare systems also associated with a significant economic costs. Alternate-day fasting (ADF) as a nutritional intervention, has demonstrated potential in relieving symptoms associated with multiple metabolic syndromes, however, its clinical applicability is limited by hypoglycemia risk and poor long-term adherence. Therefore, pharmacological interventions are still needed, for thousands of years, natural products have been extensively utilized in human disease research. This study aimed to investigate the hepatoprotective effect and underlying mechanism of BS012 (a 70 % ethanol extract of Platycodon grandiflorum, Cinnamomum cassia, and Asiasarum sieboldii mixed in the ratio of 2:2:1) in the development of NASH. 3T3-L1 adipocytes were treated with various doses of BS012 (1, 5, and 10 μg/ml). Male C57BL/6 N mice were exposed to fructose, palmitate, and cholesterol (FPC) diet, in conjunction with 42 g/l high fructose corn syrup (HFCS) water for a duration of 6 months to induce NASH. Applied ADF management or oral administration of three doses (100, 200, and 300 mg/kg) of BS012 to the mice to evaluate its effect. Serum lipid parameters, biochemical markers of liver damage, and pro-inflammatory cytokines were analyzed. Liver histological analyses were conducted to check the morphologic changes. Signaling pathways related with lipid metabolism, inflammation, apoptosis, and fibrosis in the liver were investigated using western blot. BS012 treatment effectively reduced the intracellular lipid droplets accumulated in 3T3-L1 cells. In 6 months of the dietary intervention induced NASH mice model, it was found a remarkable increment in body, liver, and perigonadal fat weight, accompanied by significantly up-regulated hepatocellular steatosis, apoptosis, inflammation, and fibrosis levels. BS012 treatment effectively reduced the growth rate of both body and organ weights, ameliorated level of serum biochemical markers associated with dyslipidemia and liver damage, and suppressed the expression of pro-inflammatory cytokines. Furthermore, BS012 treatment diminished hepatic lipid accumulation, enhanced fatty acid oxidation level, and consequently mitigated hepatic steatosis, also significantly inhibited the expression of pro-inflammatory factors, and markedly reduced apoptosis response and fibrosis progression in NASH development. The FPC diet combined with HFCS induced a NASH mouse model that closely mimics the relevant pathology of human NASH within 6 months, BS012 markedly attenuated these pathological features, with the observed protective effects attributed to the reduction of hepatic steatosis through modulation of ChREBP-α- and AMPK-mediated lipid synthesis and fatty acid oxidation pathways. In addition, BS012 suppressed the TLR-4/NF-κB signaling pathway, thereby alleviating inflammation, as well as reducing hepatic apoptosis responses, and attenuating the progression of liver fibrosis via inhibition of the TGF-β/Smad signaling pathway. The synergistic interaction among the botanical components of BS012 is believed to act on multiple molecular targets, enhancing therapeutic efficacy through complex regulatory mechanisms, which collectively contribute to the mitigation of liver injury thereby offering protection against NASH progression. BS012, a novel combination of three medicinal herbal extracts, holds promise as a potential therapeutic candidate for the treatment of NASH.

Age-related macular degeneration (AMD) is a leading cause of vision impairment in people over the age of 60. Currently, the FDA-approved drugs for AMD have various side effects, and there is a notable lack of drug development for dry AMD. This study aimed to explore the therapeutic effects of mono-ethyl fumarate (MEF) on AMD. MEF effectively protected ARPE-19 cells from cell death induced by a combination of A2E and blue light exposure. In a C57BL/6J mouse model of retinal degeneration caused by sodium iodate, MEF played a role in preserving retinal thickness and maintaining the layered structure of the retina. It was assessed via fundus imaging, optical coherence tomography, and hematoxylin and eosin staining. Treatment with MEF significantly increased the expression of antioxidant proteins such as HO-1, NQO1, and SOD1 in ARPE-19 cells. Additionally, treatment with MEF significantly increased the levels of the antioxidant proteins SOD1 and GPX4 in the mouse retina. Concurrently, it significantly reduced the levels of apoptosis-related factors, such as the Bax/Bcl-2 ratio and Caspase -3 cleavage. These findings suggest that MEF may represent a promising therapeutic candidate for the management of AMD.

Schisandrin C (SCC), a bioactive lignan compound derived from Schisandra chinensis (S. chinensis), has been demonstrated to promote intestinal health. However, the antidepressant activity of SCC and its impact on the gut‒brain axis have not been reported. This study aimed to investigate the antidepressant effects of SCC and elucidate its molecular mechanisms through modulation of the microbiota‒gut‒brain axis. Artificial intelligence (AI)-based target protein prediction, network pharmacology analysis, and experimental validation using intestinal cells, Caenorhabditis elegans, and mice models were conducted. Targeted metabolomics, gut microbiota analyses, and molecular biology techniques were employed for mechanistic elucidation. SCC treatment effectively suppressed depressive-like behaviors in mice subjected to chronic unpredictable mild stress (CUMS). SCC upregulated brain-derived neurotrophic factor (BDNF) expression in the brain by regulating the AKT/CREB/BDNF signaling pathway. Additionally, integrated network pharmacology, molecular docking, and metabolomics analyses revealed that SCC significantly increased brain serotonin levels by inhibiting monoamine oxidase (MAO) activity. Furthermore, SCC increased the abundance of Akkermansia and Bifidobacterium, as observed both in the synthetic microbial community in vitro and in the gut microbiota in vivo. Additionally, SCC effectively alleviated intestinal barrier dysfunction and reduced intestinal inflammation in vitro in intestinal cells, in vivo in C. elegans infected with Bacteroides fragilis, and in vivo in the CUMS-induced mice model. SCC improves depressive-like behaviors by modulating the microbiota‒gut‒brain axis. These findings underscore the potential of SCC as an effective therapeutic agent for depression.