Fungal drug resistance is a major health threat, and reports of clinical resistance worldwide are becoming increasingly common. In a research program to discover new molecules to help overcome this problem, 14 new lanostane-type triterpenoids, gibbosicolids A−G (2−8) and gibbosic acids I−O (9−15), were isolated from the fruiting bodies of Ganoderma gibbosum, along with seven known triterpenoid derivatives. These compounds featured high levels of oxidation, epimerization, and γ-lactonization. Structures were elucidated by comprehensive spectroscopic analyses and HRMS data. Absolute configurations were assigned based on quantum chemical calculations, including calculated chemical shift with DP4+ analysis, coupling constants, and electronic circular dichroism (ECD) methods. Results show that the calculated NMR with DP4+ analysis could not reliably establish the overall spatial configuration of molecules possessing independent and free-rotational stereoclusters. All these compounds significantly increased the sensitivity of fluconazole (FLC)-resistant C. albicans to FLC. Compounds 2, 5, 9, 12, 16, 17, and 21 exhibited strong antifungal activity against FLC-resistant C. albicans when combined with FLC, with MIC 50 values ranging from 3.8 to 8.8 μg/mL.

There is growing concern that chemotherapy drugs can damage Leydig cells and inhibit the production of testosterone. Increasing evidence shows that melatonin benefits the reproductive process. This study mainly explores the protective effect and possible molecular mechanism of melatonin regarding cisplatin-induced oxidative stress in testicular tissue and Leydig cells. We found that there were only Leydig and Sertoli cells in the testes of gastrointestinal tumor patients with azoospermia caused by platinum chemotherapeutic drugs. Melatonin (Mel) receptor 1/melatonin receptor 2 (MT1/MT2) was mainly expressed in human and mouse Leydig cells of the testes. We also observed that the melatonin level in the peripheral blood decreased and oxidative stress occurred in mice treated with cisplatin or gastrointestinal tumor patients treated with platinum-based chemotherapeutic drugs. iTRAQ proteomics showed that SIRT1/Nrf2 signaling and MT1 proteins were downregulated in cisplatin-treated mouse testes. The STRING database predicted that MT1 might be able to regulate the SIRT1/Nrf2 signaling pathway. Melatonin reduced oxidative stress and upregulated SIRT1/Nrf2 signaling in cisplatin-treated mouse testes and Leydig cells. Most importantly, after inhibiting MT1/MT2, melatonin could not upregulate SIRT1/Nrf2 signaling in cisplatin-treated Leydig cells. The MT1/MT2 inhibitor aggravated the cisplatin-induced downregulation of SIRT1/Nrf2 signaling and increased the apoptosis of Leydig cells. We believe that melatonin stimulates SIRT1/Nrf2 signaling by activating MT1/MT2 to prevent the cisplatin-induced apoptosis of Leydig cells.

A phytochemical study on the aerial parts of Leonurus japonicus led to the isolation and identification of 38 labdane diterpenoids, including 18 new (1, 2, 11, 12, 16–21, 24, 30–34, 37, 38) and 20 known (3–10, 13–15, 22, 23, 25–29, 35, 36) analogues. Their structures were elucidated based on physical data analysis, including 1D and 2D NMR, HRMS, UV, IR, and X-ray diffraction. The structure of the known compound 4 was confirmed by single-crystal X-ray diffraction data. These compounds can be divided into furanolabdane (1–10), tetrahydro­furanolabdane (11–15), lactonelabdane (16–23), labdane (24–29), and seco-labdane (30–38) type diterpenoids. All compounds were screened by lipopolysaccharide (LPS)-induced nitric acid (NO) production in RAW264.7 cells to evaluate anti-inflammatory effects. Compounds 1, 5, 10–13, 16–19, 31–33, and 38 inhibited NO production with IC50 values lower than 50 μM, with compound 30 being the most active, with an IC50 value of 3.9 ± 1.7 μM. Further studies show that compound 30 inhibits pro-inflammatory cytokine production and IKK α/β phosphorylation and restores the IκB expression levels in the NF-κB signaling pathway.

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