2024年24期封面推荐文章《如意珍宝丸临床与基础研究专题》

封面寓意：桌上放置的一柄精致玉如意，象征吉祥如意的美好祝愿；旁边的中药材如短穗兔耳草、珍珠母、红花、肉豆蔻、毛诃子、荜茇、肉桂等，则直接关联到藏药经典名方如意珍宝丸的主要组成。透过窗户可见的青藏高原壮丽雪山景色，突出了藏医药的独特魅力及其深厚的地域特色。

编者按：如意珍宝丸源自藏族药经典名方珍宝丸，由短穗兔耳草、珍珠母、红花、肉豆蔻、毛诃子、荜茇、肉桂、藏木香、人工麝香、沉香、诃子、决明子等30味药材组成，具有清热、醒脑开窍、舒筋通络、干黄水等功效，是藏族医学治疗白脉病的首选药物，在三叉神经痛、偏头痛、带状疱疹后神经痛等神经病理性疼痛、关节性疼痛及中风后遗症的治疗中具有良好的临床疗效。然而，其临床疗效特点、优势环节、药效物质与作用机制均不明确。围绕上述关键科学问题，特别编发该专题，内容包括：通过前瞻性的多中心、随机、双盲、安慰剂、平行对照临床试验，证实了如意珍宝丸对初、早期膝骨关节炎患者的西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分、视觉模拟（VAS）评分应答率、WOMAC疼痛评分、WOMAC功能评分和中医证候评分均具有良好的临床疗效，填补了该品种治疗膝骨关节炎循证证据的不足；采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法，定性解析了如意珍宝丸所含化学成分及其入血、入脑成分，为诠释其多成分、多靶点、多层次的协同作用机制奠定了数据基础；采用Ⅳ型胶原酶丘脑腹后外侧核区显微注射的方式，成功制备了小鼠卒中后中枢痛模型，并基于此开展了系列药理学实验研究，不仅明确了如意珍宝丸可有效缓解其继发性损伤和中枢痛，还证实了该品种对卒中后痛觉过敏和脊髓中枢敏化的减轻药效，进而从神经炎症角度阐释了如意珍宝丸修复神经-血管单元及调控趋化因子信号轴的作用机制；从“药效-靶标-成分-药动”多维关联视角，系统解析了如意珍宝丸在血浆或脑脊液中暴露量较高、且对神经病理性疼痛具有较强干预作用的主要效应物质甘草酸、没食子酸、芹菜素-7-O-葡萄糖醛酸苷、芹菜素，相关结果为如意珍宝丸效应物质基础的明晰及其质量标准的制定提供了可靠的实验证据。上述临床与基础研究内容有助于明确如意珍宝丸的独特疗效优势、揭示其物质基础与机体生命活动的交互作用及规律，也为解析藏族药复杂体系的作用模式提供了良好示范。该专题期冀为同行提供有价值的信息，促进民族医药的传承与发展。

Recommended Cover Article for Issue 24, 2024: "Clinical and Basic Research Topics of Ruyi Zhenbao Pills"

Cover meaning: A delicate jade ruyi placed on the table symbolizes good wishes for good luck and prosperity; The nearby Chinese medicinal herbs such as short ear rabbit ear grass, mother of pearl, safflower, nutmeg, hairy seeds, long pepper, cinnamon, etc. are directly related to the main components of the classic Tibetan medicine formula Ruyi Zhenbao Wan. The magnificent snow capped mountains of the Qinghai Tibet Plateau visible through the window highlight the unique charm of Tibetan medicine and its profound regional characteristics.

Editor's note: Ruyi Zhenbao Wan originates from the classic Tibetan medicine formula Zhenbao Wan. It is composed of 30 medicinal herbs, including short ear rabbit ear grass, mother of pearl, safflower, nutmeg, hairy hawthorn, long pepper, cinnamon, Tibetan wood fragrance, artificial musk, agarwood, hezi, and cassia seed. It has the effects of clearing heat, awakening the brain, relaxing tendons and unblocking collaterals, and drying yellow water. It is the preferred medication for the treatment of white vein disease in Tibetan medicine and has good clinical efficacy in the treatment of neuropathic pain, joint pain, and post-stroke sequelae such as trigeminal neuralgia, migraine, and postherpetic neuralgia. However, its clinical efficacy characteristics, advantageous links, active substances, and mechanisms of action are not clear. Based on the key scientific issues mentioned above, a special topic has been compiled, which includes: through prospective multicenter, randomized, double-blind, placebo-controlled, parallel controlled clinical trials, it has been confirmed that Ruyi Zhenbao Pill has good clinical efficacy in the treatment of knee osteoarthritis in patients with primary and early stages, including the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, Visual Analog Scale (VAS) score response rate, WOMAC pain score, WOMAC functional score, and Traditional Chinese Medicine syndrome score, filling the gap in evidence-based treatment of knee osteoarthritis with this variety; By using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry, the chemical components and blood and brain components of Ruyi Zhenbao Pill were qualitatively analyzed, laying a data foundation for interpreting its multi-component, multi-target, and multi-level synergistic mechanism; A mouse model of post-stroke central pain was successfully prepared by microinjection of type IV collagenase into the ventral posterior lateral nucleus of the thalamus. Based on this, a series of pharmacological experiments were conducted, which not only confirmed that Ruyi Zhenbao Pill can effectively alleviate secondary injury and central pain, but also confirmed its efficacy in reducing post-stroke hyperalgesia and spinal cord sensitization. Furthermore, the mechanism of Ruyi Zhenbao Pill in repairing neurovascular units and regulating chemokine signaling axes was explained from the perspective of neuroinflammation; From the multidimensional correlation perspective of "efficacy target composition pharmacokinetics", the main effectors of Ruyi Zhenbao Wan, such as glycyrrhizic acid, gallic acid, apigenin 7-O-glucuronide, and apigenin, which have high exposure levels in plasma or cerebrospinal fluid and strong intervention effects on neuropathic pain, were systematically analyzed. The relevant results provide reliable experimental evidence for clarifying the substance basis of Ruyi Zhenbao Wan and formulating its quality standards. The above clinical and basic research content helps to clarify the unique therapeutic advantages of Ruyi Zhenbao Pill, reveal the interaction and laws between its material basis and the body's life activities, and provide a good demonstration for analyzing the complex system of Tibetan medicine. This topic aims to provide valuable information for peers and promote the inheritance and development of ethnic medicine.