Department of Biochemistry, 117 Schweitzer Hall, University of Missouri-Columbia, Columbia, MO, 65211, USA.
Department of Medical Pharmacology and Physiology, MA 415 Medical Sciences Building, One Hospital Drive, Columbia, MO, 65212, USA.
BMC Complement Med Ther. 2020 Jan 15;20(1):9. doi: 10.1186/s12906-019-2789-9.
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.
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.
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.
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.
从 Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn.（魔鬼爪）和 H. zeyheri 的次生块茎中制备的各种药物在非洲、欧洲、美国、南美洲和其他地方销售，用于治疗关节炎、腰痛、风湿病和神经痛等炎症和肌肉骨骼疾病。尽管过去二十年进行的临床研究支持此类产品的总体安全性，但也有记录表明偶尔会出现胃肠道紊乱（腹泻、恶心、呕吐、腹痛）、头痛、眩晕和过敏（过敏）反应（皮疹、荨麻疹和面部肿胀）。用于治疗魔鬼爪产品的健康状况存在性别差异，因此，使用情况可能也存在性别差异，可能会出现副作用和潜在毒性。然而，魔鬼爪产品的毒理学研究主要在雄性动物身上进行。为了解决这一不足，我们报告了几种 Harpagophytum procumbens（HP）水醇提取物在雌性和雄性 Sprague Dawley 大鼠中的毒理学研究，这些提取物通过 UPLC-MS 进行了化学分析。
雌性和雄性 Sprague Dawley 大鼠在两组中进行了为期一个月和三个月的研究，两组大鼠的饮食中分别含有和不含有 HP 提取物，剂量为人类等效剂量（HED）的 7-10 倍。分析血清的血液化学指标，并检查心脏、肝脏、肺、肾脏、胃以及小肠和大肠的组织病理学。通过方差分析（ANOVA）和 Dunnett 检验分析血液化学指标的组间差异，对于具有边缘分布特性的终点，通过 Kruskal-Wallis 检验验证组间差异。使用卡方检验测试组织病理学的组间差异。
在两项研究中均检测到血液化学指标中存在组间与性别相关的显著差异。此外，在两项研究之间还存在一些与性别相关的差异。然而，未检测到与提取物消耗相关的显著组织病理学影响。
魔鬼爪提取物的毒理学分析导致血液化学指标中存在显著的性别相关影响。然而，根据我们的判断，在这些剂量和时间内，观察到的任何影响都不表明存在严重毒性。随后对 Harpagophytum procumbens 和其他具有类似特性的药物的毒理学和临床研究应更详细地探讨潜在性别相关影响的基础和后果。
