Traditional Chinese Medicine For Cerebral Ischemia-Reperfusion Injury

Chinese herbal medicine pair is a relatively fixed combination of two herbal flavors commonly used in clinical practice of traditional Chinese medicine. It is the basic form in the application of traditional Chinese medicine compatibility and an important bridge connecting traditional Chinese medicine and prescriptions[93]. Studies have found that many traditional Chinese medicine pairs have good anti-CIRI effects, such as Danshen-safflower medicine pair, Angelica Chuanxiong-xiong medicine pair, etc.

Danshen-Safflower Pair

Danshen safflower belongs to the traditional Chinese medicine of promoting blood circulation and removing blood stasis, and the compatibility combination of these two medicines is one of the common drug pairs in traditional Chinese medicine compound. The combination of the medicine has the effects of promoting blood circulation and removing blood stasis, stimulating menstruation and relieving pain, and is widely used in the clinical treatment of gynecology and cardiovascular diseases. In recent years, studies have found that the drug exerts anti-CIRI effects mainly by inhibiting oxidative stress and inflammatory responses, and reducing endoplasmic reticulum stress levels. Chen Yulin et al[94] selected the main active ingredients in four Danshen and safflower medicinal materials, danshensu, salvianolic acid A and B, and hydroxysafflower yellow A, as the experimental subjects to investigate the anti-CIRI effect of Danshen safflower herb pairs.

Click to cistanche tubulosa capsules for  cerebral ischemia reperfusion injury

The research results show that the drug pair can better reduce the brain tissue damage caused by cerebral ischemia-reperfusion, and it is speculated that the Danshen safflower drug pair can achieve neuroprotective effects through anti-inflammation and regulation of endoplasmic reticulum stress. Xia Ying[95] conducted research on the anti-CIRI activity and the optimal ratio of the two components of danshensu and hydroxysafflower yellow A, and the results showed that the compatibility of danshensu and hydroxysafflower yellow A (1:1) The treatment group can significantly improve the neurological function scores of the rats in the model group. In addition, another study showed that the combination of Danshen and safflower is more effective in treating CIRI than the two herbs used alone, which further explains the scientific connotation of the combination of traditional Chinese medicines [96].

Frankincense-Myrrh Pair

Both frankincense and myrrh belong to the traditional Chinese medicine of promoting blood circulation and relieving pain. After the two medicines are compatible, both qi and blood are taken into account, and the effects of promoting blood circulation and relieving pain, reducing swelling and promoting muscle growth are enhanced. Neonatal and other ways to achieve better neuroprotection. 11-carbonyl-β-acetylboswellic acid and Z-bisabolsterone are the main active ingredients of frankincense and myrrh in the treatment of CIRI. Studies have shown that the above two ingredients alone have shown a good therapeutic effect on CIRI model rats .

Wang Jitao et al[97] studied the therapeutic effect of the combined application of 11-carbonyl-β-acetylboswellic acid and Z-bisabolone, and the results showed that the combined application of the above two components can significantly reduce the neurological damage of CIRI model rats To a certain extent, it shows a certain dose-relationship, and its mechanism of action may be related to the regulation of protein expression of vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and delta-like ligand 4 (DLL4).

Astragalus-Safflower Pair

Astragalus has the effect of invigorating the middle and nourishing Qi and invigorating the spleen, and is a commonly used traditional Chinese medicine for invigorating qi in clinical practice, while safflower has the effect of promoting blood circulation, dredging menstrual flow, dispelling blood stasis and relieving pain, and is a commonly used traditional Chinese medicine for promoting blood circulation in clinical practice. Syndrome treatment has a good clinical effect. The combination of astragalus and safflower can exert anti-CIRI effect by inhibiting inflammation and oxidative stress response and promoting angiogenesis.

Literature reports that astragaloside IV and astragalus polysaccharide in Astragalus membranaceus, and hydroxysafflower yellow A in safflower all have certain protective effects on CIRI. The study found that the combined application of Astragalus and safflower in the treatment of CIRI was significantly better than that of the two herbs alone, and the anti-CIRI mechanism was related to the regulation of transforming growth factor and B-cell lymphoma-2 2, the expression of Bcl-2) is closely related to [98-99].

Angelica Chuanxiong Herbal Pair

Angelica has the effects of nourishing and activating blood, regulating menstruation and relieving pain, mainly nourishing blood, while Ligusticum chuanxiong has the effect of promoting qi, activating blood, expelling wind and relieving pain, mainly promoting qi, and combining qi and blood to enhance the effect of nourishing and activating blood. At present, the drug is widely used in gynecology and cerebrovascular diseases. The combination of Angelica and Chuanxiong can play a therapeutic role in the treatment of cerebrovascular diseases by improving neuroplasticity and maintaining the stability of the blood-brain barrier.

Lin Junbin [100] conducted research on the anti-CIRI effect of the combination of Angelica and Chuanxiong with Angelica polysaccharide and Ligustrazine as the main active ingredients. The results of the study showed that the single drug treatment group of angelica and chuanxiong, and the combination treatment group of angelica and chuanxiong could improve the neurological function of focal reperfusion injury model rats. Works best. The anti-CIRI effect of angelica and chuanxiong is related to the regulation of neuroplasticity and reduction of blood-brain barrier permeability by polysaccharides of angelica and ligustrazine.

In addition, the study found that the brain tissue of rats treated with CIRI decreased with the prolongation of the treatment time of ischemia-reperfusion injury. Therefore, it can be speculated that the recovery of the neurological function of brain tissue after ischemia-reperfusion injury may not only be treated by drugs, but also a process of self-recovery may exist.

Traditional Chinese Medicine Compound Prescription for Treatment of CIRI

Traditional Chinese medicine compound prescription is the main form of TCM clinical medicine. Studies have found that many classic famous prescriptions have anti-CIRI effects, such as Buyang Huanwu Decoction, Taohong Siwu Decoction, etc. In addition, some modern Chinese medicine compound preparations such as Mailuoning Injection and Naojianjian Granules also have a protective effect on CIRI.

Buyang Huanwu Decoction

Buyang Huanwu Decoction comes from "Yilin Gaicuo" written by Wang Qingren, a famous doctor in the Qing Dynasty. It is a classic prescription for the disease, and its clinical curative effect is definite. Buyang Huanwu Decoction can play an anti-CIRI role by inhibiting platelet activation and excessive release of glutamate, and inhibiting the toxicity of excitatory amino acids. Zhao et al[108] found that Buyang Huanwu Decoction can significantly relieve brain tissue damage caused by ischemia-reperfusion, and determined that the best treatment time window for this compound is within 4 hours of ischemia-reperfusion, suggesting that it should be used in the early stage of CIRI. The therapeutic effect of Buyang Huanwu Decoction is better. In addition, it is speculated that the curative effect of Buyang Huanwu Decoction is related to the regulation of glutamate receptors and the inhibition of glutamate release. Another study shows that Buyang Huanwu Decoction exerts anti-CIRI effect by increasing the antioxidant level of brain tissue, reducing the degree of lipid peroxidation damage, inhibiting platelet aggregation and activation, regulating PI3K/Akt signaling pathway, and promoting ischemia-reperfusion injury After the brain tissue repair and achieve [109-110].

Coptis detoxification soup

Huanglian Jiedu Decoction is a common heat-clearing agent in clinical practice. It is composed of four traditional Chinese medicines: Coptis chinensis, Scutellaria baicalensis, Cortex Phellodendron and Gardenia. Huanglian Jiedu Decoction can play an anti-CIRI role by inhibiting oxidative stress and inflammatory response, regulating energy metabolism and mitochondrial function, and inhibiting cell apoptosis. Studies have reported that baicalin and other components in Scutellaria baicalensis have good anti-CIRI effects.

Wang et al. [111] used 1H-NMR metabolomics combined with multivariate statistical analysis to comprehensively evaluate the anti-CIRI effect of Huanglian Jiedu Decoction. The 1H-NMR data of rat serum and brain tissue samples showed that Huanglian Jiedu Decoction can significantly alleviate the metabolic disorder caused by CIRI, improve the levels of metabolites such as lactic acid, glucose and creatinine, and protect mitochondrial membranes, regulate neurotransmitters and anti-inflammatory effects. Oxidation, anti-inflammation and other methods can restore brain tissue to a normal state and thus play a protective role in the brain. In addition, the protective function of Huanglian Jiedu Decoction on brain tissue injury caused by ischemia-reperfusion can also activate the expression of hypoxia-inducible factor-1α through the PI3K/Akt signaling pathway, thereby inhibiting the neural apoptosis induced by ischemia-reperfusion, etc. to achieve [112-114].

Rehmannia Yinzi

Dihuang Yinzi is a traditional prescription composed of 12 traditional Chinese medicines, including rehmannia glutinosa, Morinda officinalis, dogwood, dendrobium, cistanche, aconite, schisandra, official laurel, white poria cocos, Ophiopogon japonicus, calamus and polygala, according to the theory of traditional Chinese medicine. The effects of kidney yin, tonifying kidney yang, and resuscitating phlegm can play an anti-CIRI role by promoting the proliferation of neural stem cells, reducing oxidative stress damage, inhibiting cell apoptosis, and promoting angiogenesis. In modern clinical practice, Rehmannia Yinzi is gradually being used as one of the effective prescriptions for treating CIRI. Studies have found that Dihuang Yinzi can improve the neurological function of CIRI model rats by activating the Notch signaling pathway, which has a certain dose-related relationship [115]. Another study showed that Dihuangyinzi can also significantly increase the expression levels of Bax, Bcl-2, Caspase-3 proteins and VEGF in the brain tissue of rat models of ischemia-reperfusion injury, suggesting that Dihuangyinzi can also inhibit oxidation, Inhibit nerve cell apoptosis and promote angiogenesis to alleviate nerve function damage caused by ischemia-reperfusion [116].

Tongxinluo Capsules

Tongxinluo Capsule is a traditional Chinese medicine compound preparation made from 12 traditional Chinese medicines including ginseng, leech, scorpion, ground beetle, centipede, cicada slough, red peony root, sandalwood, borneol, balsamic incense, frankincense, and jujube seed. It has the effect of dredging collaterals and relieving pain. At present, this prescription is often used clinically to treat cardiovascular and cerebrovascular diseases. The mechanism of action of Tongxinluo Capsules in treating ischemic stroke includes inhibiting inflammatory response, improving blood-brain barrier permeability and promoting angiogenesis, etc. Gao Zhijie et al[117] used animal experiments combined with network pharmacology methods to investigate the protective effect and mechanism of Tongxinluo Capsules on CIRI. Animal experiments were evaluated with neurobehavioral scores, brain injury degree, and cerebral infarct size as indicators. The results showed that Tongxinluo Capsules had obvious protective effects on the brain tissue of CIRI rats, and there was a certain dose-related effect.

In addition, in order to further explore the chemical components and mechanism of action in Tongxinluo Capsules that really exert curative effects, 132 active ingredients and 240 genes that intersect with cerebral ischemia target genes were screened out from 12 Chinese medicines in Tongxinluo Capsules by using network pharmacology. Gene. According to the network pharmacology results, recombinant cAMP-dependent protein kinase A catalytic subunit a (protein kinase cAMP-activated catalytic subunit alpha, PRKACA), adenylate cyclase 1, dopamine D2 receptor, etc. The core gene, cAMP and cyclic guanosine monophosphate/cyclic guanosine monophosphate kinase (cyclic guanosine monophosphate, cGMP/cyclicguanosate-dependent protein kinase, PKG) are the main signaling pathways for Tongxinluo capsule to work. The in-depth study of the mechanism of action of Xinluo Capsules provides some theoretical support. In addition, studies have shown that Tongxinluo Capsules can effectively protect the blood-brain barrier, thus having a preventive effect on CIRI diseases [118].

Cistanche

Cistanche contains a variety of active ingredients such as echinacoside and acteoside, which have been shown to possess strong antioxidant and anti-inflammatory properties. When cerebral ischemia (lack of blood flow to the brain) occurs, it can lead to the accumulation of harmful free radicals and inflammation, resulting in cell damage and death.  When blood flow is restored during reperfusion, it can cause additional damage to brain tissue through an inflammatory response known as reperfusion injury.  Cistanche's active ingredients can help to mitigate these deleterious effects by neutralizing free radicals and reducing inflammation, thus protecting the brain tissue from damage and improving recovery outcomes.