The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer; however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects of an aqueous extract of Forsythia viridissima fruits (EFVF) and its major constituents. Chemical constituents from EFVF were characterized and quantified with the UHPLC-diode array detector method, and three major constituents were identified as arctiin, matairesinol, and arctigenin. The in vitro cytotoxicity was measured by the Ez-cytox viability assay, and the in vivo neuroprotection activity was evaluated by a von Frey test in two rodent animal models that were administered LOHP. EFVF significantly alleviated the LOHP-induced mechanical hypersensitivity in the induction model. EFVF also prevented the induction of mechanical hyperalgesia by LOHP in the pre- and co-treatment of LOHP and EFVF. Consistently, EFVF exerted protective effects against LOHP-induced neurotoxicity as well as inhibited neurite outgrowths in PC12 and dorsal root ganglion cells. Among the major components of EFVF, arctigenin and matairesinol exerted protective effects against LOHP-induced neurotoxicity. Therefore, EFVF may be useful for relieving or preventing LOHP-induced peripheral neuropathy in cancer patients undergoing chemotherapy with LOHP.

Forsythia viridissima fruit, one of Forsythiae Fructus (FF) is widely used in traditional medicine to treat diverse diseases-related clinical symptoms, including fever, pain, vomiting, nausea, and abscess. However, the safety of FF has not been fully assessed. In this study, we evaluated the acute oral toxicity and genotoxic potential of an aqueous extract of Forsythia viridissima fruits (EFVF). For an acute oral toxicity test, male and female SD rats (n = 5) orally received a single dose of 5000 mg/kg EFVF. The genotoxic potential of EFVF was evaluated with a battery of tests, including an in vitro bacterial reverse mutation test using five mutant strains of Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2 uvrA), an in vitro chromosomal aberration test using Chinese hamster lung (CHL/IU) cells, and an in vivo micronucleus test using bone marrow cells in male ICR mice that were orally administered EFVF. All tests were completed in compliance with Organization for Economic Cooperation and Development guidelines and/or regional regulatory standards for toxicity tests. In the acute oral toxicity test, the animals did not show any significant mortality and body weight changes for 14 days following a single dose of EFVF at 5000 mg/kg. There was no evidence of genotoxicity of EFVF based on the results of the in vitro bacterial reverse mutation test (up to 5000 μg/plate), the in vivo micronucleus test (up to 5000 mg/kg), and the in vitro chromosomal aberration test (1100-2500 μg/mL). We found that EFVF is safe with regard to acute toxicity in rats as well as genotoxicity such as mutagenesis or clastogenesis under the present experimental conditions. These results might support the safety of EFVF as a potential therapeutic material for the traditional use or pharmaceutical development.

Heart failure, a major public health issue, often stems from prolonged stress or damage to the heart muscle, leading to cardiac hypertrophy. This can progress to heart failure and other cardiovascular problems. Doxorubicin (DOX), a common chemotherapy drug, and isoproterenol (ISO), a β-adrenergic agonist, both induce cardiac hypertrophy through different mechanisms. This study investigates TongGuanWan (TGW,), a traditional herbal remedy, for its effects on cardiac hypertrophy and fibrosis in DOX-induced H9c2 cells and ISO-induced mouse models. TGW was found to counteract DOX-induced increases in H9c2 cell surface area (n = 8, p < 0.01) and improve biomarkers like ANP (n = 3, p < 0.01)) and BNP (n = 3, p < 0.01). It inhibited the MAPK pathway (n = 4, p < 0.01) and GATA-4/calcineurin/NFAT-3 signaling, reduced inflammation by decreasing NF-κB p65 translocation, and enhanced apoptosis-related factors such as caspase-3 (n = 3, p < 0.01), caspase-9 (n = 3, p < 0.01), Bax (n = 3, p < 0.01), and Bcl-2 (n = 3, p < 0.01). Flow cytometry showed TGW reduced apoptotic cell populations. In vivo, TGW reduced heart (n = 8~10, p < 0.01), and left ventricle weights (n = 6~7), cardiac hypertrophy markers (n = 3, p < 0.01), and perivascular fibrosis in ISO-induced mice, with Western blot analysis confirming decreased levels of fibrosis-related factors like fibronectin, α-SMA (n = 3, p < 0.05), and collagen type I (n = 3, p < 0.05). These findings suggest TGW has potential as a therapeutic option for cardiac hypertrophy and fibrosis.

In traditional Chinese medicine (TCM) and traditional Korean medicine (TKM), Gwakhyangjeonggi-san (GJS) is an herbal decoction used to treat gastrointestinal disorders and allergic diseases. However, no randomized controlled trials have reported the efficacy and safety of GJS against atopic dermatitis (AD) or its comorbidities. This clinical trial investigated the clinical efficacy and safety of GJS for treating patients with AD who have gastrointestinal symptoms, using a multi-omics approach that included 16S rRNA sequencing and metabolomics. This study was a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Fifty-two patients with AD (age: 19-60) were randomly assigned to receive either the GJS (N = 27) or placebo (N = 25) granules thrice daily for 8 weeks. The primary outcome was measured as the change in the SCORing of Atopic Dermatitis index from baseline to 8 weeks. The secondary outcomes included the eczema area and severity index, dermatology life quality index, EuroQoL 5 dimensions 5 levels (EQ-5D-5L), immunological factors, gastrointestinal status, and safety evaluation. In addition, 16S rRNA sequencing on gut-microbiomes and non-targeted metabolomics approach using mass spectrometry on sera samples were applied to investigate the GJS therapeutic mechanism. After 8 weeks, AD symptoms were reduced in both the GJS and placebo groups without any serious adverse events, but the reduction was not significantly different between the two groups. However, the EQ-5D-5L scores and gastrointestinal symptom scores, such as bitter-tasting fluid presenting in the mouth, upper abdomen bloating, and nausea, only improved in the GJS group. To further elucidate the effect of GJS on patients with AD who have gastrointestinal symptoms, 16S rRNA sequencing and metabolomics were executed. The GJS group had lower gut microbiome diversity including observed OUT, Ace, Chao1 and Shannon index than the placebo group at enrollment time, while the difference in gut microbiome diversity between GJS and placebo group was eliminated by 8 weeks of treatment. Consistently, the metabolomics results showed that the gut microbiome-derived uremic toxins, including indoxyl sulfate and phenylacetylglutamine, significantly increased in the placebo group, while these in GJS group were maintained without any significant change. These results showed that the GJS had no significant effect on AD compared to the placebo but exerted a beneficial effect on improving the quality of life and gastrointestinal symptoms in patients with AD, and it acted by modulating gut microbiome diversity and gut microbiome-derived uremic toxins. Our findings support the use of GJS for AD comorbidities and also provide evidence that multi-omics approaches can be useful for understanding herbal decoctions in TCM and TKM comprehensively.

This study aimed to evaluate the genotoxic potential of the fruit and seed powder, fruit puree, and aqueous extracts of Morinda citrifolia (Rubiaceae, noni). The genotoxic potential of the noni substances was evaluated using in vitro Ames, in vitro chromosomal aberration, and in vivo micronucleus tests. All test procedures were conducted per Organization for Economic Cooperation and Development guidelines, and good laboratory practice. None of the noni fruit test substances showed genotoxic signs up to 5000 and 2000 μg/plate in the Ames and micronucleus tests, respectively. In the chromosomal aberration test, neither the fruit puree nor aqueous extract showed structural and numerical aberrations up to 5000 and 4650 μg/mL, respectively, irrespective of metabolic activation, in both 6 h and 24 h treatment groups. The safe ranges of noni fruit and seed powders were up to 2500 and 2100 μg/mL, respectively, in the 6 h treatment group and up to 1600–4100 and 370–450 μg/mL, respectively, in both 6 h and 24 h treatment groups in the presence of metabolic activation. Noni fruit and seeds were safe in terms of genotoxicity under our experimental conditions. Our data are the first to provide valuable genotoxic information on Morinda citrifolia.