OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective: To analyze the safety, effectiveness, economics, innovation, suitability and accessibility of tetrandrine in the treatment of pneumoconiosis, and provide evidence-based basis for health policy decision-making and clinical practice. Methods: In July 2022, the system searched PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed databases (the retrieval time was from the establishment of the database to June 30, 2022), screened the documents that meet the standards, extracted and evaluated the data, and used the "HTA checklist" developed by the International Network of Agencies for Health Technology Assessment (INAHTA) to evaluate the HTA report. AMSTAR-2 Scale was used to evaluate the quality of systematic evaluation/Meta analysis. CHEERS Scale was used to evaluate the quality of pharmacoeconomics research. The included cohort study or case-control study was evaluated with the Newcastle-Ottawa Scale. The included randomized controlled trial (RCT) studies were evaluated using the Cochrane Risk Bias Assessment Tool (Cochrane RCT) quality evaluation criteria. Comprehensive comparison and analysis based on the characteristics of the data included in the study. Results: A total of 882 related literatures were detected from the initial screening. According to relevant standards, 8 RCT studies were finally selected for analysis. Statistical results showed that basic treatment with tetrandrine could better improve FEV(1) (MD=0.13, 95%CI: 0.06-0.20, P<0.001), FEV(1)/FVC (MD=4.48, 95%CI: 0.61-8.35, P=0.02) and clinical treatment efficiency. Tetrandrine had a low incidence of adverse reactions. The affordability coefficient of tetrandrine tablets was 0.295-0.492. Conclusion: Tetrandrine can improve the clinical symptoms and pulmonary ventilation function of pneumoconiosis patients, most of the adverse reactions are mild, and the clinical application is safe.
Humans ; Pneumoconiosis/drug therapy* ; Benzylisoquinolines/therapeutic use* ; Drugs, Chinese Herbal ; Case-Control Studies

As a member of the dibenzyl isoquinoline alkaloid family, cepharathine is an alkaloid from the traditional Chinese medicine cepharathine, which is mainly used for treatment of leukopenia and other diseases. Recent studies of the inhibitory effect of cepharathine against SARS-CoV-2 have attracted widespread attention and aroused heated discussion. As the original discoverer of the anti-SARS-CoV-2 activity of cepharanthine, here we briefly summarize the discovery of cepharanthine and review important progress in relevant studies concerning the discovery and validation of anti-SARS-CoV-2 activity of cepharathine, its antiviral mechanisms and clinical trials of its applications in COVID-19 therapy.
Antiviral Agents/therapeutic use* ; Benzylisoquinolines/therapeutic use* ; COVID-19 ; Humans ; SARS-CoV-2

Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.
Acetophenones ; pharmacology ; therapeutic use ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Benzopyrans ; pharmacology ; therapeutic use ; Benzylisoquinolines ; pharmacology ; therapeutic use ; Catechols ; pharmacology ; therapeutic use ; Heterocyclic Compounds, 4 or More Rings ; pharmacology ; therapeutic use ; Humans ; Isothiocyanates ; pharmacology ; therapeutic use ; Naphthoquinones ; pharmacology ; therapeutic use ; Neoplasms ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Signal Transduction ; drug effects

Tetrandrine (Tet), the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7A, Tet (0.3, 1 μmol·L(-1)) was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC (against PI3K, Akt, JNK, ERK, p38 MAPK and NF-κB-p65, respectively) were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac1, Cdc42, and RhoA in MH7A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Rac1, Cdc42, and RhoA, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.
Animals ; Arthritis ; Arthritis, Rheumatoid ; metabolism ; prevention & control ; Benzylisoquinolines ; pharmacology ; therapeutic use ; Cell Movement ; drug effects ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; Down-Regulation ; Fibroblasts ; drug effects ; metabolism ; Humans ; MAP Kinase Signaling System ; Phosphatidylinositol 3-Kinases ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; Protein-Serine-Threonine Kinases ; metabolism ; Signal Transduction ; Stephania ; chemistry ; Synovial Membrane ; cytology ; drug effects ; metabolism ; rac1 GTP-Binding Protein ; metabolism ; rhoA GTP-Binding Protein ; metabolism

Benzylisoquinolines ; therapeutic use ; Calcium Channel Blockers ; therapeutic use ; Combined Modality Therapy ; Humans ; Pneumoconiosis ; drug therapy ; Tablets

Aged ; Benzylisoquinolines ; therapeutic use ; Bronchoalveolar Lavage ; Female ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Phytotherapy ; Pneumoconiosis ; metabolism ; therapy ; Quality of Life ; Treatment Outcome

OBJECTIVETo observe the clinical efficacy of tetrandrine combined with acetylcysteine effervescent tablets in the treatment of silicosis.

METHODSA total of 96 patients with silicosis were randomly divided into treatment group (49 cases) and control group (47 cases). Both groups were given routine therapy including anti-inflammatory, antitussive, and antiasthmatic drugs, and the patients in treatment group were given tetrandrine combined with acetylcysteine effervescent tablets at the same time. Tetrandrine (100 mg) was orally administrated twice a day, and there was a one-day interval between every 6 days' continuous administration; totally, there were four courses of treatment, with 3 months for each course, and there was a one-month break between each course. Acetylcysteine effervescent tablets (600 mg) were taken twice a day; each course of treatment was 12 days, and there were four courses; for the first two months, there was one course per month, and then one course every other two months for the rest of time. Clinical symptoms, pulmonary ventilation function, serum superoxide dismutase (SOD) and changes in X-ray findings were observed.

RESULTSAfter treatment, the treatment group had significantly increased rates of improvements in cough, expectoration, chest congestion and pain, and dyspnea compared with the control group (P < 0.05). Compared with the control group (serum SOD level: 70.466±20.261 U/ml) and the treatment group before therapy (serum SOD level: 68.182±21.414 U/ml), the treatment group after therapy had significantly increased serum SOD level (77.389±21.315 U/ml?, forced vital capacity, and forced expiratory volume in one second (P < 0.05). Eight patients in treatment group showed improvement in the chest X-ray findings of silicosis.

CONCLUSIONThe combination of tetrandrine and acetylcysteine effervescent tablets show some effect in the treatment of silicosis. It can be an effective option for treating silicosis as there are no other specific remedies.

Acetylcysteine ; therapeutic use ; Aged ; Benzylisoquinolines ; therapeutic use ; Humans ; Male ; Middle Aged ; Silicosis ; drug therapy ; Superoxide Dismutase ; metabolism ; Treatment Outcome

OBJECTIVETo study the healing effect of pneumoconiosis with tetrandrine and massive whole-lung lavage.

METHODSChoose 34 confirmed pneumoconiosis patients as drug treatment group and complex treatment group, and 17 tested workers as control group. Collected the content of TGF-beta1 and P III P which in these three investigated groups.

RESULTSDrug treatment group and complex treatment group of patients improved the clinical symptoms and lung function Compared with Pretreatment, the FVC, FEV1.0, FEV1.0/FVC, MVV was obviously higher than those before treatment (P < 0.05). Complex treatment group than in the drug treatment group increased more significantly (P < 0.05). The level of TGF-beta1 and P III P was reduced after complex treatment (P < 0.05). Moreover,the level of TGF-beta1 and P III P in these patients are lower than in those patients treated with tetrandrine combined with whole lung lavage (P < 0.05).

CONCLUSIONTetrandrine combined with whole-lung lavage could significantly retard the development of pneumoconiosis by lessening the TGF-beta1 and P III P in serum.

Adult ; Benzylisoquinolines ; therapeutic use ; Bronchoalveolar Lavage ; Collagen Type III ; blood ; Combined Modality Therapy ; Humans ; Male ; Middle Aged ; Pneumoconiosis ; blood ; therapy ; Transforming Growth Factor beta1 ; blood ; Treatment Outcome

OBJECTIVETo observe the therapeutic efficacy of tetrandrine tablets combined with matrine injection in the treatment of silicosis.

METHODSSixty-three patients with silicosis were randomly divided into treatment group (n = 33) and control group (n = 30). Both groups received anti-inflammatory, cough-relieving, and anti-asthmatic treatment. Meanwhile, the treatment group was given tetrandrine tablets (100 mg bid) and matrine injection (150 mg qd). There were 4 courses of tetrandrine treatment (each course = 3 months), with one-month intervals among them. Matrine injection was used for 15 consecutive days in each month. There were 2 courses of matrine treatment (each course = 3 months), with a one-month interval in between. The clinical symptoms, pulmonary function, serum superoxide dismutase (SOD) activity, and chest X-ray images were observed before and after treatment.

RESULTSAfter treatment, chest distress, chest pain, shortness of breath, and other respiratory symptoms were relieved significantly (P < 0.05). The treatment group showed significantly higher SOD activity than before treatment and the control group (P < 0.05) and significantly higher forced vital capacity and forced expiratory volume in one second than before treatment and the control group (P < 0.05). After treatment, 5 patients (4 stage II cases and 1 stage III case, all in rapidly progressive forms) in the treatment group showed smaller, lighter, and clearer shadows with decreased overall intensity on chest X-ray; 12 patients showed significantly fewer and clearer lung markings on chest X-ray.

CONCLUSIONTetrandrine tablets combined with matrine injection have some therapeutic effect on silicosis.

Aged ; Alkaloids ; administration & dosage ; therapeutic use ; Benzylisoquinolines ; administration & dosage ; therapeutic use ; Humans ; Injections ; Male ; Middle Aged ; Quinolizines ; administration & dosage ; therapeutic use ; Silicosis ; drug therapy ; Tablets ; Treatment Outcome