ABSTRACT
BACKGROUND: Multiple myeloma (MM) is an incurable hematological malignancy with limited therapeutic efficacy. Eclipta prostrata is a traditional Chinese medicinal plant reported to possess antitumor properties. However, the effects of E. prostrata in MM have not been explored. PURPOSE: The aim of this study was to define the mechanism of the ethanol extract of E. prostrata (EEEP) in treating MM and identify its major components. METHODS: The pro-ferroptotic effects of EEEP on cell death, cell proliferation, iron accumulation, lipid peroxidation, and mitochondrial morphology were determined in RPMI-8226 and U266 cells. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and 4-hydroxynonenal (4HNE) were detected using western blotting during EEEP-mediated ferroptosis regulation. The RPMI-8226 and U266 xenograft mouse models were used to explore the in vivo anticancer effects of EEEP. Finally, high performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry system (UPLC-Q/TOF-MS) were used to identify the major constituents of EEEP. RESULTS: EEEP inhibited MM cell growth and induced cell death in vitro and in vivo. By promoting malondialdehyde and Fe2+ accumulation, lipid peroxidation, and GSH suppression, EEEP triggers ferroptosis in MM. Mechanistically, EEEP regulates the Keap1/Nrf2/HO-1 axis and stimulates ferroptosis. EEEP-induced lipid peroxidation and malondialdehyde accumulation were blocked by the Nrf2 activator NK-252. In addition, HPLC and UPLC-Q/TOF-MS analysis elucidated the main components of EEEP, including demethylwedelolactone, wedelolactone, chlorogenic acid and apigenin, which may play important roles in the anti-tumor function of EEEP. CONCLUSION: In summary, EEEP exerts its anti-MM function by inducing MM cell death and inhibiting tumor growth in mice. We also showed that EEEP can induce lipid peroxidation and accumulation of ferrous irons in MM cells both in vivo and in vitro, leading to ferroptosis. In addition, this anti-tumor function may be achieved by the EEEP activation of Keap1/Nrf2/HO-1 axis. This is the first study to reveal that EEEP exerts anti-MM activity through the Keap1/Nrf2/HO-1-dependent ferroptosis regulatory axis, making it a promising candidate for MM treatment.
Subject(s)
Eclipta , Ferroptosis , Heme Oxygenase-1 , Kelch-Like ECH-Associated Protein 1 , Multiple Myeloma , NF-E2-Related Factor 2 , Plant Extracts , Ferroptosis/drug effects , Kelch-Like ECH-Associated Protein 1/metabolism , Multiple Myeloma/drug therapy , Animals , NF-E2-Related Factor 2/metabolism , Humans , Plant Extracts/pharmacology , Cell Line, Tumor , Heme Oxygenase-1/metabolism , Mice , Eclipta/chemistry , Lipid Peroxidation/drug effects , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects , Mice, Nude , Mice, Inbred BALB C , Male , Antineoplastic Agents, Phytogenic/pharmacology , EthanolABSTRACT
RATIONALE: Androgenic alopecia (AGA) is a prevalent condition with progressive miniaturization of hair follicles. Currently, reliable treatments have remained limited, and complementary medications for AGA are still being investigated. Traditional Chinese medicine formulas have conspicuous advantages in the treatment of AGA with good development prospects. Zimmer aqueous spray (ZAS) is a water spray containing Zimmer herbal extract powder (ZMWP), which consists of Ligustri lucidi Fructus, Ecliptae Herba, Fallopia multiflora (Thunb.) Harald. and Polygonatum sibiricum Delar. ex Redoute, etc. ZMWP is an active ingredient in the prevention of hair loss. Our aim is to provide evidence for the effectiveness of ZAS in the treatment of AGA. PATIENT CONCERNS: A 41-year-old man had suffered from hair loss for 8 years. INTERVENTIONS: The patient with moderate AGA received 3 to 4 mL ZAS daily or every other day for 3 months. OUTCOMES: The hair density obviously increased after 3 months of therapy. The improvement of hair diameter, vellus hair rate, and 1 hair pilosebaceous unit rate were observed with a trichoscopy and quantitatively analyzed. Besides, honeycomb pigment pattern mitigated and arborized red lines. LESSONS: The results suggested that ZMWP might have the capability of improving hair growth and attenuating AGA, which can be a promising alternative treatment of AGA.
Subject(s)
Alopecia , Hair , Male , Humans , Adult , Alopecia/drug therapy , Hair Follicle , Medicine, Chinese TraditionalABSTRACT
This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.