Screening for Active Compounds of Acorus calamus against SARS-CoV-2 Viral Protease and Mechanism Prediction.

COVID-19, caused by SARS-CoV-2, has emerged as the most destructive emerging infectious disease of the 21st century. Vaccination is an effective method to combat viral diseases. However, due to the constant mutation of the virus, new variants may weaken the efficacy of vaccines. In the current field of new coronavirus research, viral protease inhibitors have emerged as a highly regarded therapeutic strategy. Nevertheless, existing viral protease inhibitors do not fully meet the therapeutic needs. Therefore, this paper turned to traditional Chinese medicine to explore new active compounds. This study focused on 24 isolated compounds from Acorus calamus L. and identified 8 active components that exhibited significant inhibitory effects on SARS-CoV-2 PLpro. Among these, the compound 1R,5R,7S-guaiane-4R,10R-diol-6-one demonstrated the best inhibitory activity with IC50 values of 0.386 ± 0.118 µM. Additionally, menecubebane B and neo-acorane A exhibited inhibitory activity against both Mpro and PLpro proteases, indicating their potential as dual-target inhibitors. The molecular docking results confirmed the stable conformations of these compounds with the key targets and their good activity. ADMET and Lipinski's rule analyses revealed that all the small molecule ligands possessed excellent oral absorption properties. This study provides an experimental foundation for the discovery of promising antiviral lead compounds.

Compliance of postoperative gastric cancer patients with oral nutritional supplementation and its influencing factors.

OBJECTIVES: To evaluate the compliance of postoperative gastric cancer patients with oral nutritional calcium supplementation and explore its influencing factors, in order to provide a reference for formulating relevant nursing interventions. METHODS: A total of 269 postoperative patients with gastric cancer admitted to the third department of surgery of the Fourth Hospital of Hebei Medical University from February to July 2020 were selected retrospectively through convenient sampling. A general information questionnaire and the Chinese version of the modified medication adherence eight-item scale were used to conduct a cross-sectional survey, in order to evaluate the compliance of postoperative gastric cancer patients with oral nutritional supplementation. RESULTS: A total of 269 questionnaires were distributed in this study, and 228 valid questionnaires were finally recovered. The compliance score for oral nutritional calcium supplements in postoperative patients with gastric cancer was (6.43±0.21). The results of multiple linear regression analysis showed that the patients' education level, family monthly average income, postoperative time, medication belief and social support were factors influencing postoperative compliance with oral nutritional supplementation (P<0.05). CONCLUSIONS: The compliance of postoperative gastric cancer patients with oral nutritional calcium supplements is at a medium to low level. Patients' education level, family monthly average income, postoperative time, medication belief, and social support are the main influencing factors. It is necessary to formulate and implement relevant interventions to improve compliance.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Simultaneous separation and quantitation of three phytosterols from the sweet potato, and determination of their anti-breast cancer activity.

The present study provides the method for simultaneous separation and determination of concentration and evaluates anti-breast cancer activity of three phytosterols from the sweet potato (Ipomoea batatas L.): daucosterol linolenate (DLA), daucosterol linoleate (DL), and daucosterol palmitate (DP). A cell viability assay revealed that the three phytosterols had a stronger inhibitory effect on MCF-7 than MDA-MB-231 breast cancer cell line, and had no effects on non-tumorigenic MCF-10A cells. In vivo experiments demonstrated that DLA, DL, and DP suppressed tumor growth in MCF-7 xenograft breast cancer model in nude mice. Given the anti-breast cancer activity of DLA, DL, and DP, an HPLC method for the determination of their content in the sweet potato was developed. The method had satisfactory linearity (R2 = 0.9992-0.9999). The limits of detection (LOD) were in the range of 2.5-10 µg/mL, the limits of quantification (LOQ) were 5-25 µg/mL, and the recovery rates were 97.64-103.02%. Additionally, the HPLC method was successfully validated in eight sweet potato cultivars. This novel technique can be applied for the determination of DLA, DL, and DP in the sweet potato.

Coptisine-induced apoptosis in human colon cancer cells (HCT-116) is mediated by PI3K/Akt and mitochondrial-associated apoptotic pathway.

BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths in the word. Coptisine (COP), an isoquinoline alkaloid derived from Coptis chinensis Franch, possesses a wide variety of pharmacological effects. However, its anti-proliferative effect on colon cancer is not fully elucidated. In the present study, we aimed to ascertain whether COP inhibits HCT-116 cell growth and to further explore the molecular mechanism in vitro and in vivo. METHODS: Cell viability was determined by MTT assay. Cell migration was detected using wound healing assay. Apoptosis, mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) was analysis via flow cytometry. Hoechst 33342 was used for morphology observation. The expression levels of proteins related to mitochondrial-mediated apoptotic pathway were detected by western blotting. In addition, the antitumor ability of COP was further measured in athymic nude mice. RESULTS: COP significantly decreased cell viability and migration in HCT-116 cells. Flow cytometry and Hoechst 33342 analysis confirmed that COP suppressed cell proliferation by inducing apoptosis. COP decreased Δψm dose-dependently and induced intracellular ROS production time-dependently. Western blotting showed that COP activated mitochondrial-associated apoptosis by down-regulating Bcl-2, Bcl-XL, pro-caspase 3, XIAP level and up-regulating Bax, Bad, cytochrome c, Apaf-1, AIF and cleaved caspase-3 expression. In addition, COP also attenuated PI3K/Akt signaling pathway. In vivo study showed that 150 mg/kg COP significantly delayed the tumor development in BALB/c nude mice. Immunohistochemical analysis also confirmed the activated apoptosis in tumor tissue. CONCLUSION: The results demonstrated that COP induces apoptosis in HCT-116 cells through PI3K/Akt and mitochondrial-associated apoptotic pathway. Our findings suggest that COP has potential to be a therapeutic candidate for colon cancer patients.

Anti-breast-Cancer Activity Exerted by ß-Sitosterol-d-glucoside from Sweet Potato via Upregulation of MicroRNA-10a and via the PI3K-Akt Signaling Pathway.

Breast cancer (BC) is a prominent source of cancer mortality in women throughout the world. ß-Sitosterol-d-glucoside (ß-SDG), a newly isolated phytosterol from sweet potato, possibly displays potent anticancer activity. However, the probable anticancer mechanisms involved are still unclear. This study sought to study how ß-SDG from sweet potato affects two BC cell lines (MCF7 and MDA-MB-231) and nude mice bearing MCF7-induced tumors. In addition, we assessed how ß-SDG affects tumor suppressor miR-10a and PI3K-Akt signaling in BC cells. Cell viability and proliferation were determined via MTT and colony-formation assays, and apoptosis was quantified by Hoechst staining and flow cytometry. In addition, miR-10a expression and apoptosis-related protein levels were measured. Our study indicated that ß-SDG exhibited cytotoxic activities on MCF7 and MDA-MB-231 cells via inducing apoptosis and activating caspase proteases in these cells. Furthermore, the experimental results in nude mice bearing MCF7-induced tumors demonstrated that oral ß-SDG administration at medium (60 mg/kg) or high (120 mg/kg) doses was sufficient to substantially impair the growth of tumors and to decrease the levels of CEA, CA125, and CA153 by 64.71, 74.64, and 85.32%, respectively, relative to those of the controls ( P < 0.01). ß-SDG was further found to regulate the expression of PI3K, p-Akt, Bcl-2-family members, and other factors involved in the PI3K-Akt-mediated mitochondrial signaling pathway via the tumor suppressor miR-10a. These findings indicated that ß-SDG suppresses tumor growth by upregulating miR-10a expression and inactivating the PI3K-Akt signaling pathway. Furthermore, ß-SDG could be developed as a potential therapeutic agent against MCF7-cell-related BC.

Role of Daucosterol Linoleate on Breast Cancer: Studies on Apoptosis and Metastasis.

The antitumor property of steroids in sweet potato ( Ipomoea batatas L.) remains poorly understood. Herein, we investigated the anticancer effect on breast carcinoma of daucosterol linoleate (DL), a steroid isolated from sweet potato. DL inhibited the cell viability of estrogen receptor (ER)-positive MCF-7 breast cancer cells at an IC50 value of 53.27 ± 9.02 µg/mL, while the effect was modest in ER-negative MDA-MB-231 breast cancer cells. Flow cytometry indicated that the DL-induced apoptosis in MCF-7 cells is dose-dependent. However, DL inhibited tumor growth and tumor weight at 100 mg/kg in MCF-7 xenograft nude mice. DL diminished the expression of Bcl-xl, Bcl-2, and XIAP, while increasing Bax, Bad, and activated caspase-dependent apoptosis in tumor tissues. Furthermore, DL inactivated the upstream Pi3k/Akt/NF-κB pathway. In the 4T1 spontaneous metastasis model, DL blocked metastasis progression, decreased the number of visible metastasis foci and inhibited metastasis size distribution in lung tissue. Further studies showed that DL suppressed VEGF, MMP 2, and MMP 9 expression in both tumor and lung tissues. From these results, we can assume that DL is a potential adjuvant therapy for ER-positive breast cancer patients.

8-Cetylberberine inhibits growth of lung cancer in vitro and in vivo.

AIMS: This study is aimed at detecting the anti-tumor efficacy of a new berberine (BBR) derivative 8-cetylberberine (HBBR), which has a significant improvement in hydrophobicity and pharmacological effects compared to BBR. MAIN METHODS: The human non-small lung cancer cell line A549 and normal human lung epithelial cells (MRC-5) were cultured to observe inhibition in vitro. Cell viability was analyzed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of HBBR on cell cycle arrest and apoptosis were assessed by flow cytometry and western blotting. In animal studies, BALB/c nude mice were subcutaneously injected with A549 cells in the armpit and administrated with different dose of HBBR and BBR. The body weight, organ coefficient and tumor inhibitory rate were recorded to evaluate the effect of HBBR in vivo. KEY FINDINGS: The data showed that HBBR induced G1-phase cycle arrest by interfering with the expression of Cyclins D1 and Cyclin E1, increased apoptosis by inducing caspase pathway, and probably inhibited the PI3K/Akt pathway in A549 cells. In addition, animal experiments proved that oral administration of HBBR at a dose of 10mg/kg could significantly inhibit tumor growth, which is stronger than the 120mg/kg dose of BBR treatment. SIGNIFICANCE: Our results suggest that HBBR showed a significantly higher anti-tumor efficacy than BBR in vitro and in vivo and could be a potential therapy for lung cancers.

[A new sesquiterpene from Acorus calamus (â ¡)].

A new quaiane-tgpe sesquiterpene was isolated from the 95% ethanol extract of the rhizomes of Acorus calamus by silica gel and sephadex LH-20 column chromatographic methods. Structure and absolute configuration of the sesquiterpene were elucidated by spectroscopic data and X-ray crystallographic analysis, and named as 1R,5R,7S-guaiane-4R,10R-diol-6-one.