1.Intervention Effect of Ruyi Zhenbao Pills on Mice with Central Pain After Thalamic Stroke
Kexin JIA ; Gejia ZHONG ; Chunyan ZHU ; Luochangting FANG ; Xiaoxiao WANG ; Tengteng XU ; Zhixing HU ; Cairen JUEJIA ; Xianda HU ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):82-89
ObjectiveTo observe the intervention effect of Ruyi Zhenbao pills (RYZBP) on central pain after thalamic stroke in mice and explore the underlying mechanism. MethodThe central post-stroke pain syndrome (CPSP) model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group, a model group, low-, medium-, and high-dose RYZBP groups (0.65, 1.3, 2.6 g·kg-1), and a pregabalin group (0.075 g·kg-1). Seven days after modeling, the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass, once per day for 25 days, while those in the sham group and the model group received an equal volume of normal saline. During this period, mechanical pain and cold pain were detected at different time points, and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology, and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay (ELISA). ResultCompared with sham operation group, mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed (P<0.01). TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1α (IL-1α) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum, while the expressions of Ang-2, granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly (P<0.01). Compared with model group, RYZBW dose groups significantly increased mechanical pain threshold, decreased cold sensitivity pain threshold, decreased hypothalamus cell apoptosis ratio (P<0.01), decreased the expression of IL-1α and CCL5 in hypothalamus tissue and serum, while the expression of ANG-2, G-CSF and IL-4 were significantly increased (P<0.05). ConclusionRYZBP can relieve hyperalgesia in CPSP mice, and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1α, CCL5, IL-4, G-CSF, and Ang-2.
2.Expert Consensus on Clinical Application of Ruyi Zhenbaowan
Ming CHEN ; Jingling CHANG ; Shangquan WANG ; Gejia ZHONG ; Qiang DENG ; Hongxia CHEN ; Qien LI ; Yaming LIN ; Zujian XU ; Changkuan FU ; Yuer HU ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):173-183
Osteoarthritis (OA) and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan, a classic prescription in Tibetan medicine, have the functions of clearing heat, awakening the brain and opening orifices, relaxing tendons and promoting meridian circulation, and eliminating yellow water. Clinically, they are used to treat osteoarthritis, post-stroke sequelae, neuropathic pain, and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory, analgesic, and nerve-repairing effects. However, current research remains insufficient regarding the appropriate indications, timing, and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use, a panel of national experts, including clinical specialists, Tibetan medicine practitioners, pharmacologists, and methodologists, formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan, including therapeutic indications, dosage and administration, treatment duration, and medication safety. The consensus specifically addresses the clinical efficacy, appropriate timing of administration, dosage strategies, treatment cycles, and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke, reduce medication-related risks, and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine, with the standard number GS/CACM 369-2024.