Journal of Natural Medicines最新文献

In the preliminary screening, falcarinol and falcarindiol, C₁₇ polyacetylenes from the roots of Glehnia littoralis F. Schmidt ex Miq (Umbelliferae), displayed cytotoxic activity both against oxaliplatin-sensitive/resistant colorectal cancer (CRC) and gefitinib-sensitive/resistant non-small cell lung cancer (NSCLC) cells. In this study, 13 polyacetylenes including a new (3R,11R)-11-hyroxy-isofalcarinolone (1) were isolated from G. littoralis, and the chemical structures were elucidated through NMR, HRMS, and optical rotation analysis as well as DP4 plus calculation. (3S,8S)-Oplopandiol (5) showed cytotoxic activities against oxaliplatin-sensitive and -resistant CRC (HCT116 and HCT116-OxR) cells. Unexpectedly, (3R,8S)-falcarindiol (3) and (3S)-falcarinol (12), newly purified from G. littoralis, did not show cytotoxic activity. It was confirmed that both falcarinol and falcarindiol, previously evaluated, were decomposed, which seems to be the cause of inconsistent biological results. These findings indicated that C₁₇ polyacetylene could be a good starting compound for the development of anticancer leads against drug-resistant CRC and NSCLC cells, however, the stability of C₁₇ polyacetylens should be considered for further studies.

Thioredoxin-interacting protein (TXNIP), as a pivotal protein in the cellular stress response, plays a significant role in the progression of diabetic nephropathy (DN). Consequently, therapeutic strategies aimed at targeting TXNIP may offer novel interventions for patients with DN. Our study is to explore the therapeutic potential of targeting TXNIP in mitigating renal tubular injury induced by hyperglycemia. Cell viability and apoptosis of renal tubular epithelial cells (RTECs) were evaluated using CCK-8, Annexin V/7-AAD, and TUNEL staining after exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with TXNIP inhibitors (Xanthohumol, Xan). Furthermore, histochemical staining was utilized to assess the morphological changes in the kidney. Xan was determined to be a potential inhibitor of TXNIP due to its low binding energy value of - 7.433 kcal/mol. Both genetic inhibition of TXNIP using sh-RNA and pharmacological inhibition with Xan were found to reverse HG-induced RTEC apoptosis and inflammatory response. In diabetic mice, administration of Xan resulted in significant improvements in pathological features such as tubular atrophy, tubular injury score, and collagen deposition in the tubulointerstitium. Additionally, treatment with Xan effectively reduced the up-regulation of TXNIP protein expression caused by hyperglycemia. In conclusion, Xan, as a bioactive natural product, has been shown to attenuate hyperglycemia-induced renal tubular injury in both in vitro and in vivo models, potentially through the inhibition of TXNIP expression. Xan has the potential to serve as a therapeutic compound for the treatment of DN.

Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients. We aimed to explore the potential effect of red ginseng (RG) on niraparib-induced myelosuppression and to further reveal its possible molecular mechanism. Female C57BL/6 mice were divided into control, tumor, model, and RG groups (n = 6). After receiving ID8 ovarian cancer cell inoculation, the mice received niraparib treatment (80 mg/kg) for 3 days. Meanwhile, RG groups (100 and 200 mg/kg) were intragastrically treated with RG extract for 7 days. Compared with the model group, RG extract increased the counts of peripheral blood cells and enhanced the hematopoietic function of bone marrow. Furthermore, RG extract increased the colony yield of hematopoietic progenitor cells (HPCs), facilitated DNA damage repair, alleviated the G0/G1 phase cell cycle arrest, and significantly reversed the increased expression levels of p53, p21, and p27, while stimulating cyclinE1 expression levels. These findings indicate that RG might have therapeutic potential on niraparib-induced myelosuppression, which encourages further clinical trials. This study is the first to explore the efficacy and mechanism of RG in preventing myelosuppression induced by niraparib.

Ipomoea alba L. (Convolvulaceae) is an annual vine native to tropical America that is cultivated primarily for ornamental purposes. Its seeds are used in traditional medicine as a laxative, and young shoots are consumed as food. In this study, ten new resin glycosides, ipoalbins I (1)-X (10), were isolated from I. alba seeds. The structures of 1-10 were determined based on spectroscopic data. All compounds had intramolecular cyclic ester structures (jalapins). The sugar moieties in 1-10 were partially acylated by organic acids, including isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids. Notably, one of these compounds has a rare jalapin structure characterized by an ester linkage between the carboxyl group of the aglycone moiety and the hydroxyl group of an organic acid attached to the sugar moiety. In contrast, other compounds exhibited typical macrolactone structures. Furthermore, the cytotoxic activity of 1-10 against HL-60 human promyelocytic leukemia cells and their antiviral activity against herpes simplex virus type 1 (HSV-1) were evaluated. All tested compounds, except 3, were comparable to or slightly less cytotoxic than cisplatin, the positive control. In addition, all the compounds showed anti-HSV-1 activity; notably, 5 showed an EC₅₀ value lower than that of acyclovir, the positive control. However, the selectivity indices of these compounds were lower than that of acyclovir.

The traditional post-harvest processing method of Angelica acutiloba roots, which involves hanging the roots outdoors after being harvested, is known to promote the conversion of starch in roots into sucrose, thereby increasing sweetness. At the same time, this method increases the dilute ethanol-soluble extract (DEE) content in A. acutiloba roots to meet the standard set by the Japanese Pharmacopoeia 18th edition. However, in Hokkaido, where A. acutiloba has been cultivated in recent years, it is a challenge to practice this traditional post-harvest processing method owing to the risk of freezing. Therefore, it is necessary to determine post-harvest processing conditions to increase DEE content in A. acutiloba roots in Hokkaido. In this study, we cultivated seedlings in plug trays and the open field in Hokkaido and stored the harvested products at various temperatures and durations to determine changes in DEE content. DEE content immediately after harvest was 20.5% in roots from plug-tray seedlings and 27.8% in roots from seedlings cultivated in the open field. DEE content in roots stored at 0 °C increased slowly over 5 weeks, whereas that in roots stored at 20 °C increased rapidly. We found a strong correlation between DEE content and sucrose content, but not (Z)-ligustilide content. Our findings on the post-harvest processing conditions for roots revealed that the optimal post-harvest processing conditions are storage at 0 °C for at least two weeks during which DEE content increases stably, similar to the traditional method.

Oxidative stress has been implicated as a causative factor for the development and progression of osteoporosis(OP). Ellagic acid (EA), a natural polyphenol, presents anti-oxidative and anti-inflammatory properties. However, EA's role and molecular mechanism in osteoblasts have not yet been elucidated. In this study, exogenous supplementation with EA restored the osteoporotic bone defects in ovariectomized (OVX)-induced osteoporotic mice. Also, EA inhibited the H₂O₂-induced apoptosis of primary osteoblasts, prevented the production of reactive oxygen species, and restored the bone-forming potential of osteoblasts. Furthermore, EA was revealed to activate Sirtuin1 (SIRT1) and its downstream Nrf2/Heme Oxygenase 1 (HO-1) signaling pathway, and EX527 (a SIRT1 inhibitor) partially counteracted the effect of EA on bone loss. The findings suggest that EA protects against osteoporotic bone loss by activating SIRT1 and its downstream Nrf2/HO-1 signaling pathway, providing novel insights into the potential of EA as a treatment agent for osteoporosis-related bone metabolism diseases.

Radiotherapy is a primary treatment method for lung cancer, and radiation-induced lung injury has been widely studied. However, the lung and intestines are closely related, and patients receiving lung radiotherapy often experience gastrointestinal reactions. Huanglian Decoction has proven effective in treating intestinal diseases, but its role in radiation-induced intestinal injury in lung cancer has not yet been demonstrated. The study investigated the potential protective mechanisms of Huanglian Decoction against radiation-induced intestinal injury in lung cancer. In vivo experiments were conducted to examine the morphological changes. Changes in endoplasmic reticulum stress-related proteins were assessed using electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. In vitro studies involved the overexpression of TRPA1 protein in NCM460 cells via lentiviral vectors. Tumor-bearing mice exhibited severe damage to both lung and colon tissues following radiotherapy, with elevated levels of IL-33, increased expression of ST2L and TRPA1 in colon tissues, higher levels of endoplasmic reticulum stress-related proteins, and the presence of apoptosis and inflammatory responses. Huanglian Decoction reduced radiation-induced intestinal injury by lowering IL-33 levels, which in turn reduced endoplasmic reticulum stress response in colon tissues. In TRPA1-overexpressing NCM460 cells, Huanglian Decoction decreased TRPA1 expression levels and significantly alleviated endoplasmic reticulum stress response. Conclusively, the results indicate that Huanglian Decoction alleviates radiation-induced intestinal endoplasmic reticulum stress by reducing IL-33 levels, subsequently inhibiting the expression of ST2L and TRPA1 in colon tissues. This demonstrates the protective effect of Huanglian Decoction on the intestines during lung cancer radiotherapy, highlighting its promising clinical application in radiation protection.

Alzheimer disease (AD) is the most common type of dementia and accounts for the largest proportion of dementia cases. The amyloid cascade hypothesis is known for the pathogenesis of AD, in which excessive accumulation of amyloid-β (Aβ) leads to the formation of senile plaques and ultimately to AD. Inhibition of β-secretase (BACE1) may contribute to the treatment of AD by suppressing Aβ production. In this study, we isolated and characterized the activity of new and known BACE1-inhibiting compounds from two mushrooms of the Boletales order, Suillus bovinus and Boletinus cavipes, using a BACE1-inhibitory activity-guided separation approach. Three compounds (1-3) were isolated from Suillus bovinus CHCl₃ extract and three compounds (4-6) were isolated from Boletinus cavipes CHCl₃ extract. Compound 1 was a new compound. The structures were elucidated using MS, IR, and NMR. Compounds 1-6 showed BACE1-inhibitory activity (IC₅₀; 21.2, 17.8, 1.0, 1.6, 23.7, and 22.8 μM, respectively). To examine the structure-activity relationship, we also evaluated the activity of geranylgerniol, farnesol, 2,5-dihydroxy-1,4-benzoquinone and mesaconic acid. These compounds showed no activity, and these results indicate that chain terpenes alone do not show BACE1-inhibitory activity, but only when mesaconic acid or a quinone with a hydroxyl group is bound. In addition, the mode of inhibition of 2 and 3 were competitive and 4 was uncompetitive inhibition, respectively, as determined by analysis of Lineweaver-Burk and Dixon plots.

The number of patients with Alzheimer's disease (AD) is expected to increase as the population ages. The amyloid cascade hypothesis is proposed as the pathogenic mechanism of AD. We report the isolation and structural determination of three new p-terphenyl compounds, thelephantin P (1), thelephantin Q (2), and thelephantin R (3), with four known compounds (4-7), from the fruiting bodies of Thelephora aurantiotincta Corner. We evaluated Aβ aggregation and BACE1 inhibitory activities and neuroprotective activities of these isolated compounds. Compound 1 was shown to be multi-inhibitors for AD. Compound 1 had an IC₅₀ = 12.9 μM (Aβ), 6.3 μM (BACE1), and EC₅₀ = 8.0 μM (neuroprotection), respectively. Therefore, these compounds are potential therapeutic agents for AD.

Castanopsis genus (Fagaceae) were rich in plant polyphenols and often used as medicinal plants. In this study, two new lignan dimer compounds with anti-inflammatory activity and four known compounds were isolated and identified from 80% methanolic extract of Castanopsis chinensis leaves. The structure determination supported by computational chemistry and extensive spectroscopic analysis. Two new lignan dimer compounds significantly inhibited LPS-induced NO production in RAW 264.7 cells at 10 µM without cytotoxicity.