An Integrated Analysis of Network Pharmacology and Experimental Validation to Reveal the Mechanism of Chinese Medicine Formula Naotaifang in Treating Cerebral Ischemia-Reperfusion Injury

Yang, Tong; Chen, Xiangyu; Mei, Zhigang; Liu, Xiaolu; Liao, Jun; Deng, Yuewen; Ge, Jinwen

doi:10.2147/dddt.s328837

Cited by 22 publications

(11 citation statements)

References 89 publications

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“…We performed a series of investigations to evaluate the pharmacology, efficacy, and safety of NTF for more than 20 years. Studies indicate that NTF and its extracts minimize the cerebral infarct size and improve neurological function by inhibiting inflammation, oxidative stress, and apoptosis (Liao et al, 2015;Lan et al, 2020;Yang et al, 2021;Zhao et al, 2021). Considering the shared pathogenesis pathways between HT-CSVD and ischemic stroke, and if HT-CSVD is not treated in time, it can gradually progress to stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies indicate that NTF alleviates nerve damage and improves cognitive function by suppressing neuronal cell ferroptosis (Lan et al, 2020). This reduces the infarct volume and apoptotic neuronal cells as well as increases the density of dendritic spines and survival of neurons (Yang et al, 2021). One pharmacological study reports that the metabolic pathway regulated by NTF is mainly purine metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…The Chinese medicine Naotaifang (NTF) is the addition and subtraction of the classic formula--Buyang Huanwu Decoction, composed of four herbs: Astragalus mongholicus Bunge (Fabaceae) (Huangqi) 40 g, Conioselinum anthriscoides 'Chuanxiong' (Apiaceae) (Chuanxiong) 15 g, Pheretima aspergillum (Dilong) 15 g, and Bombyx Batryticatus (Jiangcan) 10 g. Single herbal medical effect and compound clinical efficacy show that NTF nourishes Qi, activates blood circulation, removes blood stasis, dredging channels, and collaterals (He et al, 2001;Lan et al, 2020;Yang et al, 2021;Xu et al, 2022). Our previous studies indicate that NTF alleviates nerve damage and improves cognitive function by suppressing neuronal cell ferroptosis (Lan et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial

Fang

Zhou

et al. 2023

Front. Pharmacol.

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Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25–30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease.Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively.Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research.Clinical Trial registration:www.chictr.org.cn, identifier ChiCTR1900024524.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial

Fang

Zhou

et al. 2023

Front. Pharmacol.

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“…It was reported that Tongxinluo (TXL) also has anti-apoptotic cerebral ischemia protection by means of the Cx43/Calpain II/Bax/caspase-3 pathway, contributing to the prevention and therapy of I/R injury (Cheng et al, 2017). Additionally, Naotaifang (NTF) was detected to increase the expression level of Bcl-2 and decrease the expression level of Bax (Yang et al, 2021a). To further study the effect of Gualou Guizhi decoction (GLGZD) on MCAO I/R injury, the involved mechanism was mainly relevant to regulating PARP-1/AIF signal pathway (Nan et al, 2020).…”

Section: Active Ingredients Of Traditional Chinese Medicinementioning

confidence: 99%

Therapeutic targets by traditional Chinese medicine for ischemia-reperfusion injury induced apoptosis on cardiovascular and cerebrovascular diseases

Cheng

Hu²,

Liu³

et al. 2022

Front. Pharmacol.

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Traditional Chinese medicine (TCM) has a significant role in treating and preventing human diseases. Ischemic heart and cerebrovascular injuries are two types of diseases with different clinical manifestations with high prevalence and incidence. In recent years, it has been reported that many TCM has beneficial effects on ischemic diseases through the inhibition of apoptosis, which is the key target to treat myocardial and cerebral ischemia. This review provides a comprehensive summary of the mechanisms of various TCMs in treating ischemic cardiovascular and cerebrovascular diseases through anti-apoptotic targets and pathways. However, clinical investigations into elucidating the pharmacodynamic ingredients of TCM are still lacking, which should be further demystified in the future. Overall, the inhibition of apoptosis by TCM may be an effective strategy for treating ischemic cardio-cerebrovascular diseases.

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“…Using the PubChem (https://pubchem.ncbi.nlm.nih.gov/) database [11], all validated compounds collected were converted into standard Canonical SMILES format, and the SMILES format files were imported into SWISS (http://www. swisstargetprediction.ch/) [12]and the Superpred website (http://prediction.charite.de/), and set the property "homo sapiens" to predict the targets of the compounds.…”

Section: Prediction Of Potential Targetsmentioning

confidence: 99%

A computer simulation-based study on the intervention of active ingredients of Mongolian medicine into the S-protein of SARS-CoV-2-associated variant Omicron

Bao

Morigentu

et al. 2022

Preprint

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BACKGROUND: Omicron VOC (BF.7) is a variant of SARS-CoV-2 that is currently spreading globally as a dominant strain. BF.7 is more infectious than existing Omicron variants, and to date there are no specific therapeutic agents for this variant. METHODS: The active compounds were collected by TCMSP, ETCM database and literature mining method, and the targets of the compounds were searched by Swiss Target Prediction and SUPERPRED database, while the targets of Omiron virus were collected by DisGeNET and GEO database, and then the intersecting targets were compared and analyzed. In this study, Swiss-Model was applied to construct the Spike RBD structure of Omicron variant BF.7 by replacing mutant amino acids into the Native Spike (S) structure, and the structural changes of Native S were compared. The four active compounds screened were docked with Omicron S protein and Omicron S-hACE2 complexes. To evaluate the structural stability of the complexes in a physiological environment, we also performed molecular dynamics simulations of the docked complexes and compared them to the control drug, chloroquine. The affinity of ligands and protein complexes was determined by free energy analysis using the MM-PBSA algorithm, and the structural changes of S proteins in combination with ligands were evaluated. RESULTS: A total of 12 mongolic medicines were screened and 310 active ingredient predictions were made, with a total of 55 genes overlapping with Omicron variants and 14 targets with the largest differences being conserved. Once these 14 targets were mapped to the active ingredients of 12 mongolic herbs, four more precise active ingredients were filtered out. Of these four phytochemicals, Berberine was the most potent inhibitor of Omicron S protein. In addition, molecular docking simulations revealed that Berberine can bind stably to Omicron S protein and the Omicron S-hACE2 complex. Using molecular dynamics simulations, Berberine was shown to be able to form a stable complex with Omicron S in a physiological environment with better results than the control drug chloroquine. Free energy analysis by the MM-PBSA algorithm and evaluation of S protein structural changes following ligand binding also demonstrated a higher affinity of Berberine for Omicron S compared to the other small molecule compounds. CONCLUSION: Berberine was found to have the most substantial inhibitory potential against Omicron VOC (BF.7) S protein and could be further investigated and developed as a potential inhibitor of Omicron.

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An Integrated Analysis of Network Pharmacology and Experimental Validation to Reveal the Mechanism of Chinese Medicine Formula Naotaifang in Treating Cerebral Ischemia-Reperfusion Injury

Cited by 22 publications

References 89 publications

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial

Therapeutic targets by traditional Chinese medicine for ischemia-reperfusion injury induced apoptosis on cardiovascular and cerebrovascular diseases

A computer simulation-based study on the intervention of active ingredients of Mongolian medicine into the S-protein of SARS-CoV-2-associated variant Omicron

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