Jian Wang

Background: Bovis Calculus (BC), also named Niuhuang in Chinese, is utilized as a resuscitation drug in Traditional Chinese Medicine (TCM) for the treatment of neurological disorders. Ischemic stroke (IS) is a significant global public health issue that currently lacks safe and effective therapeutic drugs. Ongoing efforts are focused on identifying effective treatment strategies from Traditional, Complementary, and Integrative Medicine. Noticeably, BC has been used in TCM for thousands of years to prevent or treat IS-related diseases.Methods: The historical origins of BC in the treatment of IS were investigated through the examination of ancient Chinese medical texts. Furthermore, the chemical components of BC were analyzed, and its mechanisms of action against IS were summarized using literature sourced from databases such as Web of Science, PubMed, and China National Knowledge Infrastructure. Information on Chinese medicine preparations and clinical reports was also integrated to provide an overview of modern applications and safety considerations.Results: BC mainly includes chemical components such as bile pigments, bile acids, cholesterol, proteins amino acids, and trace elements. Additionally, the efficacy of BC in treating cerebral ischemia/reperfusion injury (CI/RI) is certain, particularly due to the components of bile pigments, bile acids, and amino acids that can interfere with the enzymatic cascade reaction of CI/RI through multiple components, targets, and pathways. The active components of BC exert neuroprotective effects by reducing microcirculation disturbance, excitatory amino acid toxicity, and oxidative stress injury in the acute stage; inhibiting inflammatory injury, apoptosis, and blood-brain barrier (BBB) disruption in the subacute stage; and promoting angiogenesis and neurogenesis in the restoration stage. Furthermore, as a crude drug, BC appears in many Chinese patent medicine (CPM) preparations for the treatment of IS, and clinical and preclinical studies have proved its safety.Conclusion: The use of BC in the treatment of IS has a long history, proven efficacy, and widespread application. Future efforts should focus on elucidating its mechanisms of action and exploring its applications.

Our previous study showed l‐borneol reduced cerebral infarction in the acute stage after cerebral ischemia, but there is little about the study of subacute phase. We herein investigated the cerebral protective effects of l‐borneol on neurovascular units (NVU) in the subacute phase after transient middle cerebral artery occlusion (t‐MCAO). The t‐MCAO model was prepared by the line embolus method. Zea Longa, mNss, HE, and TTC staining were used to evaluate the effect of l‐borneol. We evaluated the mechanisms of l‐borneol on inflammation, p38 MAPK pathway, and apoptosis, etc. through various technologies. l‐borneol 0.2, 0.1, 0.05 g·kg⁻¹ could significantly reduce cerebral infarction rate, alleviate the pathological injury, and inhibit inflammation reaction. l‐borneol could also significantly increase brain blood supply, Nissl bodies, and the expression of GFAP. Additionally, l‐borneol activated the p38 MAPK signaling pathway, inhibited cell apoptosis, and maintained BBB integrity. l‐borneol had a neuroprotective effect, which was related to activating the p38 MAPK signaling pathway, inhibiting inflammatory response and apoptosis, and improving cerebral blood supply to protect BBB and stabilize and remodel NVU. The study will provide a reference for the use of l‐borneol in the treatment of ischemic stroke in the subacute phase.

Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R–Ankrd1–P53 signaling pathway.

Background: Cisplatin (CDDP) is commonly used to treat non-small cell lung cancer (NSCLC), but the appearance of drug resistance greatly hinders its efficacy. Borneol may promote drug absorption; however, synergism between borneol and CDDP in suppressing NSCLC is not clearly understood. Hence, we investigated borneol as a novel chemosensitizer to support chemotherapeutic efficacy and reduce side effects. Methods: We compared viability after exposure to d-borneol, l-borneol, and synthetic borneol in two NSCLC cell lines, A549 and H460, and selected the most sensitive cells. We then assessed synergy between borneol forms and CDDP in cisplatin-resistant NSCLC cells, H460/CDDP. Next, we identified effective concentrations and exposure times. Subsequently, we evaluated cell migration via wound healing and cell proliferation via clone formation assay. Then, we focused on P-glycoprotein (P-gp) function, cell cycle, apoptosis, and RNA sequencing to elucidate underlying molecular mechanisms for synergy. Finally, we used an H460/CDDP xenograft tumor model to verify antitumor activity and safety in vivo. Data were examined using one-way analysis of variance (ANOVA) for multiple datasets or t-test for comparisons between two variables. Results: d-Borneol was more effective in H460 than A549 cells. d-Borneol combined with CDDP showed greater inhibition of cell proliferation, migration, and clone formation in H460/CDDP cells than CDDP alone. RNA sequencing (RNA-seq) analysis identified differentially expressed genes enriched in cell cycle pathways. The impact of d-borneol on CDDP chemosensitivity involved arrest of the cell cycle at S phase via p27/p21-mediated cyclinA2/D3-CDK2/6 signaling and activation of intrinsic apoptosis via p21-mediated Bax/Bcl-2/caspase3 signaling. Further, d-borneol ameliorated drug resistance by suppressing levels and activity of P-gp. Cotreatment with d-borneol and CDDP inhibited tumor growth in vivo and reduced CDDP-caused liver and kidney toxicity. Conclusions: d-Borneol increased the efficacy of cisplatin and reduced its toxicity. This compound has the potential to become a useful chemosensitizer for drug-resistance NSCLC.