Progress of medicinal plants and their active metabolites in ischemia-reperfusion injury of stroke: a novel therapeutic strategy based on regulation of crosstalk between mitophagy and ferroptosis.

The death of cells can occur through various pathways, including apoptosis, necroptosis, mitophagy, pyroptosis, endoplasmic reticulum stress, oxidative stress, ferroptosis, cuproptosis, and disulfide-driven necrosis. Increasing evidence suggests that mitophagy and ferroptosis play crucial regulatory roles in the development of stroke. In recent years, the incidence of stroke has been gradually increasing, posing a significant threat to human health. Hemorrhagic stroke accounts for only 15% of all strokes, while ischemic stroke is the predominant type, representing 85% of all stroke cases. Ischemic stroke refers to a clinical syndrome characterized by local ischemic-hypoxic necrosis of brain tissue due to various cerebrovascular disorders, leading to rapid onset of corresponding neurological deficits. Currently, specific therapeutic approaches targeting the pathophysiological mechanisms of ischemic brain tissue injury mainly include intravenous thrombolysis and endovascular intervention. Despite some clinical efficacy, these approaches inevitably lead to ischemia-reperfusion injury. Therefore, exploration of treatment options for ischemic stroke remains a challenging task. In light of this background, advancements in targeted therapy for cerebrovascular diseases through mitophagy and ferroptosis offer a new direction for the treatment of such diseases. In this review, we summarize the progress of mitophagy and ferroptosis in regulating ischemia-reperfusion injury in stroke and emphasize their potential molecular mechanisms in the pathogenesis. Importantly, we systematically elucidate the role of medicinal plants and their active metabolites in targeting mitophagy and ferroptosis in ischemia-reperfusion injury in stroke, providing new insights and perspectives for the clinical development of therapeutic drugs for these diseases.

The Chinese Herb Codonopsis pilosula Isolate Isorhapontigenin protects against oxidative stress injury by inhibiting the activation of PI3K/Akt signaling pathway.

We investigated the effects of the Chinese herb Codonopsis pilosula isolate isorhapontigenin on antioxidant factor and the PI3K/Serine/Akt signaling pathway in Parkinson's disease. This research was, therefore, carried out to explore a possible protective mechanism of isorhamnetin in Parkinson's disease. The results support that isorhapontigenin could effectively inhibit isorhapontigenin restored myeloperoxidase + induced reduction of antioxidant levels. Also, 1-Methyl-4-phenylpyridine up-regulated the expression of phosphorylated-Akt, phosphorylated-PI3K, and phosphorylated mammalian target of rapamycin, while isorhapontigenin inhibited the expression of phosphorylated-Akt, phosphorylated-PI3K, and phosphorylated- mammalian target of rapamycin. Furthermore, LY294002 improved the antioxidant effect of isorhapontigenin in PC12 cells, and insulin-like growth factor 1 inhibited the antioxidant effect of isorhapontigenin in PC12 cells. Our results support the finding that isorhamnetin enhanced the antioxidant effect induced by 1-Methyl-4-phenylpyridine in PC12 cells by suppressing the activation of the PI3K/Akt signaling pathway.

[Assessment of efficacy of acupuncture combined with hyperbaric oxygen therapy for patients with delayed encephalopathy of CO intoxication by magnetic resonance voxel incoherent motion imaging].

OBJECTIVE: To observe the effect of acupuncture plus hyperbaric oxygen (HBO) on cerebral blood perfusion in patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP). METHODS: Twenty-eight patients with DEACMP were randomly divided into acupuncture group (n=14 cases) and control group (n=14 cases). Patients of the acupuncture group were treated by using "Xingnao Kaiqiao" needling technique (specific set of acupuncture points as Yintang ï¼»EX-HN3ï¼½, Shangxing ï¼»GV23ï¼½, Baihui ï¼»GV20ï¼½, Sishenchong ï¼»EX-HN1ï¼½, Fengchi ï¼»GB20ï¼½, Taichong ï¼»LR3ï¼½, etc., and strong stimulation) combined with HBO in an air pressurized tank, and those of the control group treated by simple HBO. The treatment was conducted once a day, 5 days a week for 6 weeks. All the patients underwent head routine magnetic resonance imaging (MRI) and intravoxel incoherent motion imaging(IVIM) scan before and after the treatment. The values of pseudo-diffusion coefficient D (D*) and perfusion fraction (f) of the bilateral semi-oval centers were measured by using MITK software package to calculate the ave-rage fD* value (f×D*). The Barthel index (BI) score was used to assess the patients' daily living ability, and the correlation between parameter values was evaluated by Pearson method. RESULTS: After the treatment, the values of f, fD* and BI scores were significantly increased in both acupuncture group and control groups (P<0.05). The values of the 3 indexes were significantly higher in the acupuncture group than those in the control group (P<0.05). The values of f and fD* were positively correlated with BI score (P<0.05), with the correlation coefficients being 0.822, 0.636 and 0.601, respectively between the fD* and f, BI and f, and BI and fD*. CONCLUSION: Acupuncture combined with HBO can significantly improve the low-perfusion of bilate-ral semi-oval center and daily living ability in patients with DEACMP, being significantly superior to simple HBO therapy in the curative effect.

[Evaluation of the efficacy of acupuncture combined with hyperbaric oxygen on delayed neuropathological sequelae after carbon monoxide poisoning by using mTI-ASL imaging].

OBJECTIVE: Quantitative assessment of white blood flow in semi-oval center of patients with delayed neuropathological sequelae (DNS) after carbon monoxide poisoning treated with acupuncture combined with hyperbaric oxygen (HBO) based on magnetic resonance multi-inversion time arterial spin labeling imaging (mTI-ASL), and to evaluate its efficacy indirectly. METHODS: Twenty-six patients with clinically diagnosed DNS were randomly divided into an observation group (13 cases) and a control group (13 cases). The conventional therapy combined with HBO were given in the control group. In the observation group,on the base of the treatment, Xingnao Kaiqiao acupuncture was applied, the main acupoints were Shuigou (GV 26), Neiguan (PC 6), Baihui (GV 20), Shangxing (GV 23), Yintang (GV 29), Sanyinjiao (SP 6) on the affected side, Sishencong (EX-HN 1), Fenglong (ST 40), Lianquan (CV 23) and Jinjin (EX-HN12) for slurred speech, Jianyu (LI 15), Waiguan (TE 5) and Shousanli (LI 10) for upper limb pain, Huantiao (GB 30), Yanglingquan (GB 34), Yinlingquan (SP 9) for lower limb pain, the treatment was given once every day, 5 days as one course, with an interval of 2 days between the course. The treatment for 6 courses was required. The conventional head MR scan, mTI-ASL and diffusion tensor imaging (DTI) scans before and 1 week after treatment were adopted, Matlab (R2014b), Mricron and Syngo.via software were adopted to measure the cerebral blood flow (CBF) and anisotropy (FA) values of the semi-oval center. The correlation between the parameters was evaluated by Pearson method. And the simple intelligent mental state examination scale (MMSE) was uesd to assess cognitive function. RESULTS: After treatment, the CBF, MMSE scores in both groups and FA values in the observation group were higher than those before treatment (P<0.05). After treatment, the CBF, FA and MMSE scores in the observation group were significantly higher than those in the control group (P<0.05). There was a positive correlation between CBF, FA and MMSE scores (P<0.05), and the correlation between CBF and MMSE was the best (r =0.822). CONCLUSION: Acupuncture combined with hyperbaric oxygen can significantly improved early white matter hypoperfusion and improved cognitive function score in patients with DNS. The curative effect is better than that of hyperbaric oxygen therapy alone. The mTI-ASL imaging can quantitatively evaluate its curative effect.

[Current state of researches on mechanisms of acupuncture in improvement of hypoxia-ischemic diseases of the central nervous system].

Acupuncture is widely used in the treatment of ischemic diseases of the central nervous system in different clinical stages and has achieved a good clinical effect. The current research showed that acupuncture can improve cerebral blood flow perfusion via increasing blood flow volume, blood flow velocity, the levels of vasomotor substances and reduction of blood viscosity and erythrocyte aggregation index. In recent years, many studies focused on the pathophysiological mechanism of acupuncture in improving cerebral ischemia via triggering the cholinergic vasodilatation, up-regulation of expression of vascular-related proteins and genes，attenuation of inflammatory reaction, etc. Currently, the methods for evaluating the effect of acupuncture are mostly noninvasive functional magnetic resonance imaging in healthy subjects. Future studies should include united selection of acupoints and acupuncture needle manipulations, more reasonable combination of different acupoints, united outcome evaluative standards, better repeatability, employment of big data, etc.