BACKGROUND A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil's Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil's Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil's Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS. METHODS Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7-10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett's test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis. RESULTS Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected. CONCLUSION Toxicologic analysis of Devil's Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.

中文翻译：

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Harpagophytum procumbens subsp. 水醇提取物的毒理学研究。 procumbens (Burch.) DC.Ex Meisn。 （Pedaliaceae）雌性和雄性大鼠。


背景技术由 Harpagophytum procumbens subsp. 的次生块茎制备的多种医药产品。 procumbens (Burch.) DC.ex Meisn。 (Devil's Claw) 和 H. zeyheri 在非洲、欧洲、美国、南美等地销售，用于治疗炎症和肌肉骨骼疾病，如关节炎、腰痛、风湿病和神经痛等。过去二十年进行的研究支持了此类产品的总体安全性，记录了罕见的胃肠道紊乱（腹泻、恶心、呕吐、腹痛）、头痛、眩晕和超敏（过敏）反应（皮疹、荨麻疹和面部肿胀）。魔鬼爪产品的使用健康状况存在与性别相关的差异，因此使用可能同样与性别相关，因此可能存在副作用和潜在毒性。然而，魔鬼爪产品的毒理学研究主要是在雄性动物身上进行的。为了解决这一缺陷，我们报告了对雌性和雄性大鼠的几种 H. procumbens (HP) 水醇提取物的毒理学研究，并通过 UPLC-MS 进行化学分析。方法 对雌性和雄性 Sprague Dawley 大鼠进行为期 1 个月和 3 个月的研究，各组的饮食不同，饮食中不含和含有 HP 提取物，剂量为人类当量剂量 (HED) 的 7-10 倍。对血清进行血液化学分析，并对心脏、肝脏、肺、肾、胃以及小肠和大肠组织进行组织病理学检查。通过采用 Dunnett 检验的 ANOVA 分析治疗组的血液化学差异，并使用 Kruskal-Wallis 检验验证具有边际分布特性的终点的显着组差异。 使用卡方分析测试组织病理学的组间差异。结果 在这两项研究中均检测到了血液化学中与性别相关的显着差异。此外，研究之间还存在一些与性别相关的差异。然而，没有检测到与提取物消耗相关的显着组织病理学影响。结论 魔鬼爪提取物的毒理学分析对血液化学产生显着的与性别相关的影响。然而，根据我们的判断，观察到的影响均未表明在这些剂量和持续时间下存在严重毒性。随后对 H. procumbens 和其他具有类似特性的药物进行的毒理学和临床研究应更详细地探讨潜在的性别相关影响的基础和后果。