Laboratorio de Neurofarmacología de Productos Naturales de La Dirección de Investigaciones en Neurociencias Del Instituto Nacional de Psiquiatría Ramón de La Fuente Muñiz, Ciudad de México, Mexico.
Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, Mexico.
J Ethnopharmacol. 2021 Mar 25;268:113550. doi: 10.1016/j.jep.2020.113550. Epub 2020 Nov 3.
Mexico is considered an ancestral center of diversity of Salvia species, however many of them lack scientific information. Salvia circinnata Cav. (syn. Salvia amarissima Ortega) is an endemic species used in traditional medicine to treat disorders attributed to a cold state like anxiety in the central nervous system, as well as gastrointestinal ailments and pain relief.
To give preclinical evidence about the pharmacological properties of this species by investigating its antinociceptive and anti-inflammatory effects, the chemical nature of at least one metabolite, and a possible mechanism of action and adverse effects, using different experimental models of pain.
Different crude extracts of Salvia circinnata Cav. aerial parts were prepared using increasing polarity and evaluated in the formalin test in mice. This screening allowed to select and evaluate an ethyl acetate extract (EtOAc), as the most bioactive extract, and a metabolite. Antinociceptive and anti-inflammatory activities were confirmed using the plantar test and carrageenan-induced edema. The antinociceptive effects of the extracts were compared to that observed with morphine (1 mg/kg), tramadol (20 mg/kg) or indomethacin (20 mg/kg) as reference drugs. Participation of opioids and TRPV1 receptors was investigated, as well as acute toxicity and adverse effects of sedation and gastric damage.
EtOAc (0.1-10 mg/kg) of S. circinnata Cav. showed a dose-dependent and significant antinociceptive activity, associated in part with the presence of a neo-clerodane glycoside amarisolide A (0.01-1 mg/kg), in the neurogenic and inflammatory phases of the formalin test. Central action of both treatments was corroborated in the plantar test, whereas anti-inflammatory effects were confirmed with the extract (1 and 10 mg/kg) and amarisolide A (1 mg/kg) in the carrageenan-induced edema test. An opioid mechanism in both treatments, and the TRPV1 receptor modulation in the extract were involved. No acute toxicity and adverse effects were noticed with the extract and pure compound in comparison to the reference drugs.
These results provide preclinical evidence of the ethnopharmacological antinociceptive S. circinnata Cav. properties, in which the neo-clerodane diterpene glycoside amarisolide A was partially responsible involving the participation of the opioid receptors, while TRPV1 receptor modulation was implicated in the anti-inflammatory activity may be because of the presence of other constituents. This information supports the use of this species in folk medicine for pain therapy.
墨西哥被认为是 Salvia 物种多样性的一个古老中心，但其中许多物种缺乏科学信息。Salvia circinnata Cav.（同义词：Salvia amarissima Ortega）是一种地方特有物种，在传统医学中用于治疗与寒冷状态相关的疾病，如中枢神经系统的焦虑，以及胃肠道疾病和疼痛缓解。
通过研究其镇痛和抗炎作用、至少一种代谢物的化学性质以及可能的作用机制和不良反应，为这种物种的药理学特性提供临床前证据，使用不同的疼痛实验模型。
使用不同的极性制备 Salvia circinnata Cav. 的不同粗提取物，并用小鼠福尔马林试验进行评价。这种筛选允许选择和评价乙酸乙酯提取物（EtOAc），作为最具生物活性的提取物，并评价一种代谢物。使用足底试验和角叉菜胶诱导的水肿来确认镇痛和抗炎活性。将提取物的镇痛作用与吗啡（1 mg/kg）、曲马多（20 mg/kg）或吲哚美辛（20 mg/kg）作为参考药物进行比较。研究了阿片类和 TRPV1 受体的参与，以及镇静和胃损伤的急性毒性和不良反应。
S. circinnata Cav. 的 EtOAc（0.1-10 mg/kg）显示出剂量依赖性和显著的镇痛活性，部分与新的 clerodane 糖苷 amarisolide A（0.01-1 mg/kg）的存在有关，在福尔马林试验的神经源性和炎症性阶段。两种治疗方法的中枢作用在足底试验中得到了证实，而在角叉菜胶诱导的水肿试验中，提取物（1 和 10 mg/kg）和 amarisolide A（1 mg/kg）证实了抗炎作用。两种治疗方法均涉及阿片类机制，而提取物涉及 TRPV1 受体调节。与参考药物相比，提取物和纯化合物均未出现急性毒性和不良反应。
这些结果为 S. circinnata Cav. 的民族药理学镇痛特性提供了临床前证据，其中 neo-clerodane 二萜糖苷 amarisolide A 部分负责涉及阿片受体的参与，而 TRPV1 受体调节可能与其他成分的存在有关。这些信息支持将该物种用于民间医学治疗疼痛。
