检索问题
姜黄素及其衍生物目前相关制剂进展如何？是否有进入临床阶段的药物？
姜黄素及其衍生物的制剂研发取得了显著进展，并且在多个临床试验中展现出潜力，尤其是在改善生物利用度方面。以下是关于姜黄素及其衍生物制剂进展和临床阶段药物的详细情况：
1. 姜黄素的生物利用度问题及解决方案
姜黄素，是黄金香料姜黄（Curcuma longa）的活性成分，具有抗氧化、抗炎和抗癌等多种药理作用，并在体外和体内研究中显示出对多种疾病的治疗潜力，包括癌症、心血管疾病、关节炎等 。然而，天然姜黄素的临床有效性受到其生物利用度低和代谢迅速的限制 。临床前数据和I期临床研究表明，口服姜黄素后肠道吸收量少、肝脏首过效应明显以及一定程度的肠道代谢是其全身生物利用度差的主要原因 。
为了克服这些障碍，研究人员在过去十年中开发了多种新型药物制剂方法来提高姜黄素的生物利用度，包括：
- 纳米颗粒 (Nanoparticles)：用于提高吸收和靶向性 。
- 脂质体封装 (Liposomal encapsulation)：能将姜黄素包裹在磷脂双层中，提高水溶性和稳定性，从而改善生物利用度 。
- 胶束 (Micelles)：利用胶束系统携带姜黄素，增加其在水性环境中的溶解度 。
- 固体分散体 (Solid dispersions)：通过将姜黄素分散在聚合物基质中来提高其溶解速率和口服生物利用度 。
- 乳剂 (Emulsions)：包括微乳剂和纳米乳剂，可以促进姜黄素的吸收 。
- 微球 (Microspheres)：用于控制姜黄素的释放，延长其在体内的作用时间 。
- 胶囊、片剂和粉末 (Capsules, tablets, and powder)：是常见的口服给药形式，但通常需要更高剂量以克服生物利用度问题 。
这些新型制剂的出现显著增强了姜黄素的生物利用度，并且一些高生物利用度的姜黄素制剂已在临床试验中展现出良好效果，证明生物利用度问题并非姜黄素临床应用的不可逾越的障碍 。
2. 姜黄素及其衍生物在临床阶段的药物应用
姜黄素及其提取物（通常包含姜黄素和其他姜黄素类化合物）已在多项临床试验中进行研究，用于治疗多种疾病。虽然很少有证据直接表明有“药物”进入了正式的临床审批阶段并获得广泛批准，但这些临床试验的结果为姜黄素作为一种补充剂或辅助治疗方案的潜力提供了支持。以下是姜黄素在不同疾病领域的临床研究进展：
2.1. 关节炎和肌肉骨骼疾病
- 骨关节炎 (Osteoarthritis, OA)：多项随机对照试验 (RCTs) 和荟萃分析显示，姜黄素和姜黄提取物可以改善骨关节炎患者的炎症和疼痛水平 。
- 一项涉及15项RCTs和1621名参与者的荟萃分析发现，与安慰剂相比，姜黄提取物和姜黄素能显著降低视觉模拟评分 (VAS) 和西方安大略和麦克马斯特大学骨关节炎指数 (WOMAC) 的疼痛、功能和僵硬评分 。
- 与非甾体抗炎药 (NSAIDs) 相比，姜黄素和姜黄提取物在缓解关节疼痛、改善功能和僵硬方面效果相似，且不良事件发生率更低 。
- 姜黄素与NSAIDs联合使用，可进一步降低VAS和WOMAC评分，且不增加不良事件 。
- 一项为期8周、双盲、安慰剂对照研究显示，每日两次服用500毫克标准化姜黄素提取物（Curcugen）显著降低了膝关节骨关节炎患者的KOOS膝关节疼痛评分和数字膝关节疼痛评分，并改善了运动功能 。
- 与布洛芬（1200毫克/天）相比，姜黄（Curcuma domestica）提取物（1500毫克/天）在膝关节骨关节炎患者的疼痛减轻和功能改善方面效果相当，且胃肠道不良事件发生率更低 。
- 姜黄素、黑胡椒和生姜的联合补充剂在降低慢性膝关节骨关节炎患者的前列腺素E2 (PGE2) 水平方面与萘普生相似 。
- 类风湿性关节炎 (Rheumatoid Arthritis, RA)：姜黄素在治疗类风湿性关节炎方面也显示出临床益处，可以改善疾病活动度评分（DAS28）、降低炎症水平（如C反应蛋白和红细胞沉降率）以及改善氧化应激 。一项包含47项RCTs的系统评价和荟萃分析指出，姜黄素是多种可能改善RA症状的膳食多酚之一 。
- 强直性脊柱炎 (Ankylosing Spondylitis, AS) 和 幼年特发性关节炎 (Juvenile Idiopathic Arthritis, JIA)：虽然初步研究显示姜黄素可能有改善作用，但需要更多的RCTs来明确其效果 。
2.2. 糖尿病和代谢疾病
- 2型糖尿病 (Type 2 Diabetes Mellitus, T2DM)：姜黄素在T2DM的预防和管理中引起了广泛关注 。
- 在动物模型中，姜黄素提取物可以延缓糖尿病的发展、改善β细胞功能、预防β细胞死亡并降低胰岛素抵抗 。
- 一项随机、双盲、安慰剂对照试验（n=272）发现，为期12个月的姜黄素干预（1500毫克/天）显著降低了2型糖尿病患者的空腹血糖和糖化血红蛋白（HbA1c），并改善了β细胞功能（HOMA-β）、降低了胰岛素抵抗（HOMA-IR）和体重，且副作用极少 。
- 姜黄素还被发现可以增加脂联素水平，降低瘦素水平，这与改善胰岛素敏感性相关 。
- 姜黄素被认为具有抗氧化、心脏保护、抗炎、抗微生物、肾脏保护、抗肿瘤、肝脏保护、免疫调节和降血糖等多种作用，这些都有助于T2DM的管理 。
- 非酒精性脂肪肝病 (Non-alcoholic Fatty Liver Disease, NAFLD)：姜黄素补充剂能够降低NAFLD患者的肝酶、炎症细胞因子、血脂水平和胰岛素抵抗，并改善NAFLD评分 。
- 多囊卵巢综合征 (Polycystic Ovary Syndrome, PCOS)：一项随机双盲安慰剂对照临床试验显示，姜黄素（500毫克，每日三次）治疗12周后，PCOS患者的空腹血糖和脱氢表雄酮水平显著降低，雌二醇水平也有非显著性升高，提示姜黄素可能有助于改善PCOS相关的雄激素过多症和高血糖 。
2.3. 炎症性疾病
- 炎症性肠病 (Inflammatory Bowel Disease, IBD)：姜黄素可能对IBD患者具有疗效，尽管现有研究的质量和方法学局限性较高 。在溃疡性结肠炎 (UC) 和克罗恩病 (CD) 的RCTs中，姜黄素和姜黄素提取物显示出改善临床或实验室结果的潜力 。
- 溃疡性结肠炎 (Ulcerative Colitis, UC) 和 克罗恩病 (Crohn's Disease)：多项RCTs显示姜黄素和姜黄提取物可改善UC和CD的临床结果 。
- 银屑病 (Psoriasis)：姜黄素和姜黄提取物在治疗银屑病方面显示出良好的临床疗效 。
- 口腔扁平苔藓 (Oral Lichen Planus)：虽然有研究表明姜黄素对口腔扁平苔藓的改善作用，但荟萃分析并未显示出其疗效 。
- 眼部炎症疾病 (Inflammatory eye diseases)：初步研究支持姜黄素的有效性 。
- 慢性胰腺炎 (Chronic pancreatitis)：初步研究支持姜黄素的有效性 。
- 胃炎和消化性溃疡 (Gastric inflammation, peptic ulcer, gastric ulcer)：姜黄素对这些状况显示出保护作用 。
2.4. 癌症
- 姜黄素在癌症研究中显示出抗癌作用，尽管大多数数据来自体外实验和动物模型 。少数临床研究的结果表明，姜黄素可能在临床肿瘤学中具有应用潜力，但仍需进一步高质量的临床试验，特别是在精确披露姜黄素制剂方面 。
2.5. 神经认知和神经系统疾病
- 阿尔茨海默病和认知衰退 (Cognitive decline and neurological diseases)：体外实验显示姜黄素能调节与神经病学相关的重要生理通路，但体内研究结果尚不一致 。新兴的姜黄素制剂正在克服生物利用度和稳定性限制，并开始在动物模型和双盲、安慰剂对照临床试验中显示出治疗认知衰退的潜力 。
- 偏头痛 (Migraine)：初步研究显示姜黄素作为预防性治疗可能有效，但许多研究的偏倚风险较高，需要进一步高质量研究 。
2.6. 其他疾病
- 高脂血症 (Hyperlipidemia)：初步研究支持姜黄素的有效性 。
- 狼疮性肾炎 (Lupus nephritis) 和 系统性红斑狼疮 (Systemic Lupus Erythematosus, SLE)：少数RCTs显示姜黄素可能改善临床结果，但需要更多研究 。
- 多发性硬化症 (Multiple Sclerosis, MS)：少数RCTs显示姜黄素可能改善临床结果，但需要更多研究 。
- Behcet氏病 (Behcet’s disease, BD) 和 大动脉炎 (Arteritis)：仅有少量RCTs，初步结果显示改善，但需要更多高质量研究 。
3. 临床研究的局限性和未来方向
尽管姜黄素在临床研究中展现出广泛的治疗潜力，但许多研究仍存在局限性：
- 研究质量和数量：许多领域的研究由于RCTs的质量较低或数量较少，其结论需要谨慎解读 。例如，在关节炎、自身免疫性疾病和消化系统疾病领域，仍然需要更多高质量、大样本、多中心的临床试验来验证或修正现有结论 。
- 制剂多样性：研究中使用的姜黄素制剂和剂量差异很大，这使得不同研究之间难以进行比较 。未来的研究应系统评估不同姜黄素制剂和剂量，以确定最佳方案 。
- 生物利用度“迷思”：尽管姜黄素的生物利用度曾被认为是主要问题，但临床试验结果表明，通过使用更高浓度或新型制剂，姜黄素仍能发挥显著的治疗作用，这表明其在特定疾病（如消化道疾病或局部作用）中可能不需要高全身生物利用度 。
总结
姜黄素及其衍生物的制剂研发已取得了显著进展，尤其是在通过各种新型制剂（如纳米颗粒、脂质体、胶束等）改善其生物利用度方面。这些进展使得姜黄素能够在临床试验中被更有效地评估。
目前，姜黄素及其提取物作为辅助治疗或补充剂，在多个疾病领域（特别是骨关节炎、类风湿性关节炎、2型糖尿病、非酒精性脂肪肝病和炎症性肠病）的临床试验中显示出积极的疗效和良好的安全性 。它被认为是一种安全且具有潜在益处的补充剂，尤其在某些情况下其疗效可与传统药物相媲美，且副作用较少 。
然而，尽管前景广阔，但姜黄素及其衍生物尚未有被正式批准为处方药物的明确证据。大多数研究将其定位为“补充剂”或“辅助治疗”。未来的研究需要更高质量、大样本、多中心、设计严谨的临床试验，并标准化姜黄素制剂和剂量，以进一步确证其临床疗效和安全性，并可能最终推动其进入更正式的药物审批流程。
References
1Efficacy and Safety of Curcumin and Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.PubMed
Liuting Zeng, Tiejun Yang, Kailin Yang, et al.
BACKGROUND: Modern pharmacological research found that the chemical components of are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis. METHODS: Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis. RESULTS: Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA. CONCLUSION: Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
2Therapeutic roles of curcumin: lessons learned from clinical trials.PubMed
Subash C Gupta, Sridevi Patchva, Bharat B Aggarwal
Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.
3Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment.PubMed
Francesca Pivari, Alessandra Mingione, Caterina Brasacchio, et al.
Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. The multifactorial nature of the pathology makes patient management, which includes lifelong drug therapy and lifestyle modification, extremely challenging. It is well known that T2DM is a preventable disease, therefore lowering the incidence of new T2DM cases could be a key strategy to reduce the global impact of diabetes. Currently, there is growing evidence on the efficacy of the use of medicinal plants supplements for T2DM prevention and management. Among these medicinal plants, curcumin is gaining a growing interest in the scientific community. Curcumin is a bioactive molecule present in the rhizome of the plant, also known as turmeric. Curcumin has different pharmacological and biological effects that have been described by both in vitro and in vivo studies, and include antioxidant, cardio-protective, anti-inflammatory, anti-microbial, nephro-protective, anti-neoplastic, hepato-protective, immunomodulatory, hypoglycaemic and anti-rheumatic effects. In animal models, curcumin extract delays diabetes development, improves β-cell functions, prevents β-cell death, and decreases insulin resistance. The present review focuses on pre-clinical and clinical trials on curcumin supplementation in T2DM and discusses the peculiar mechanisms by which curcumin might ameliorate diabetes management.
4Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials.PubMed
Timothy M Panknin, Carol L Howe, Meg Hauer, et al.
Medicinal properties of turmeric ( L.), a plant used for centuries as an anti-inflammatory, are attributed to its polyphenolic curcuminoids, where curcumin predominates. Although "curcumin" supplements are a top-selling botanical with promising pre-clinical effects, questions remain regarding biological activity in humans. To address this, a scoping review was conducted to assess human clinical trials reporting oral curcumin effects on disease outcomes. Eight databases were searched using established guidelines, yielding 389 citations (from 9528 initial) that met inclusion criteria. Half focused on obesity-associated metabolic disorders (29%) or musculoskeletal disorders (17%), where inflammation is a key driver, and beneficial effects on clinical outcomes and/or biomarkers were reported for most citations (75%) in studies that were primarily double-blind, randomized, and placebo-controlled trials (77%, D-RCT). Citations for the next most studied disease categories (neurocognitive [11%] or gastrointestinal disorders [10%], or cancer [9%]), were far fewer in number and yielded mixed results depending on study quality and condition studied. Although additional research is needed, including systematic evaluation of diverse curcumin formulations and doses in larger D-RCT studies, the preponderance of current evidence for several highly studied diseases (e.g., metabolic syndrome, osteoarthritis), which are also clinically common, are suggestive of clinical benefits.
5The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis.PubMed
Liuting Zeng, Ganpeng Yu, Wensa Hao, et al.
OBJECTIVE: To assess the efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis (OA). METHODS: The databases such as Pubmed and Cochrane Library were searched to collect the article about Curcuma longa extract and curcumin in the treatment of OA. Then, randomized controlled trials (RCTs) were selected and their data were extracted. Finally, the RevMan5.3 was utilized for risk of bias assessment and meta-analysis, the STATA15.0 were utilized for publication bias assessment, and GRADE tool were used for the evidence quality assessment of primary outcomes. RESULTS: A total of 15 RCTs involving 1621 participants were included. (1) Compared with placebo, Curcuma longa extract and curcumin (C.) can decrease the visual analog scale (VAS) and The Western Ontario and McMaster Universities (WOMAC) score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, Curcuma longa extract and curcumin are comparable with those of placebo. (2) Compared with non-steroidal anti-inflammatory drugs (NSAIDs), Curcuma longa extract and curcumin have similar effects on joint pain, function and stiffness. The incidence of adverse events in Curcuma longa extract and curcumin was lower. (3) Compared with the NSAIDs group, C.+NSAIDs can also decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, the addition of Curcuma longa extract and curcumin to NSAIDs did not increase adverse events. CONCLUSION: Curcuma longa extract and curcumin may be a safer and effective supplement for OA patients. It is recommended to use Curcuma longa extract and curcumin supplement for OA patients for more than 12 weeks.
6Herbal treatments for migraine: A systematic review of randomised-controlled studies.PubMed
Adrian L Lopresti, Stephen J Smith, Peter D Drummond
Herbal treatments are often used as a treatment for migraine. Therefore, an evaluation of their safety and efficacy is important. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and Cochrane Collaboration's tool for assessing the risk of bias, a systematic literature review of randomised, controlled human trials assessing the effects of herbal treatments delivered as a single ingredient for the acute or prophylactic treatment of migraine were conducted. Studies were identified through electronic database searches on Medline (Pubmed), Cochrane Library, Scopus, and CINAHL. Nineteen studies were identified examining the effects on migraine of feverfew, butterbur, curcumin, menthol/peppermint oil, coriander, citron, Damask rose, chamomile, and lavender. Overall, findings on the efficacy of feverfew were mixed and there was positive, albeit limited evidence for butterbur. There were positive, preliminary findings on curcumin, citron, and coriander as a prophylactic treatment for migraine, and the use of menthol and chamomile as an acute treatment. However, the risk of bias was high for many studies. The results of this systematic review suggest that several herbal medicines, via their multifactorial physiological influences, present as potential options to enhance the treatment of migraine. However, further high-quality research is essential to examine their efficacy and safety as a treatment for migraine.
7Curcumin extract improves beta cell functions in obese patients with type 2 diabetes: a randomized controlled trial.PubMed
Metha Yaikwawong, Laddawan Jansarikit, Siwanon Jirawatnotai, et al.
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression. OBJECTIVE: To assess the efficacy of improving type 2 diabetes (T2DM). STUDY DESIGN: This randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes. METHODS: All subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention. RESULTS: After 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001. CONCLUSIONS: A 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial. TRIAL REGISTRATION: Thai clinical trials regentrify no.20140303003.
8Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials.PubMed
Liuting Zeng, Tiejun Yang, Kailin Yang, et al.
OBJECTIVE: To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. METHODS: Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet 's disease (BD) involves one RCT, Crohn 's disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ' s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs. CONCLUSION: Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.
9Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials.PubMed
Zhiyong Long, Wang Xiang, Qi He, et al.
OBJECTIVE: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). METHODS: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software. RESULTS: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events. CONCLUSION: Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.
10Herbal formulation "turmeric extract, black pepper, and ginger" versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial.PubMed
Motahar Heidari-Beni, Amir R Moravejolahkami, Pegah Gorgian, et al.
Osteoarthritis is the most common articular disease that can lead to chronic pain and severe disability. Curcumin-an effective ingredient in turmeric with anti inflammatory property-plays an important role in protecting the joints against destructive factors. Gingerols and piperine, are the effective ingredients of ginger and black pepper, which may potentially enhance and sustain the effect of curcumin in this direction. To determine the effect of cosupplementation with turmeric extract, black pepper, and ginger on prostaglandin E (PGE ) in patients with chronic knee osteoarthritis, compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis (Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks. PGE was evaluated by ELISA method. 24-hr recall was also assessed. All of participants completed the study. PGE decreased significantly in both groups (p < .001), but there was no significant differences between groups. The results of this study indicated that intake of the selected herbs twice a day for 4 weeks may improve the PGE levels in patients with chronic knee osteoarthritis similar to Naproxen drug.
11An Investigation into the Effects of a Curcumin Extract (Curcugen) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study.PubMed
Adrian L Lopresti, Stephen J Smith, Shavon Jackson-Michel, et al.
Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen) or placebo. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee pain ratings, Japanese Orthopaedic Association Score for Osteoarthritic Knees (JOA), PROMIS-29, and performance-based testing comprising the 40-m fast-paced walk test, 6-min walk test, timed up-and-go test, and 30-s chair stand test. Compared to the placebo, curcumin significantly reduced the KOOS knee pain score ( = 0.009) and numeric knee pain ratings ( = 0.001). Curcumin was also associated with greater improvements ( ≤ 0.05) than the placebo on the timed up-and-go test, 6-min walk test, and the JOA total score; but not the 30-s chair stand test or 40-m fast-paced walk test. Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo. The findings support the potential efficacy of curcumin for the treatment of osteoarthritis of the knee but studies of longer duration, varying treatment doses, differing curcumin extracts, and the use of other objective outcome measures will be helpful to expand on these findings.
12Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial.PubMed
Javad Heshmati, Ashraf Moini, Mahdi Sepidarkish, et al.
BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.
13Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study.PubMed
Vilai Kuptniratsaikul, Piyapat Dajpratham, Wirat Taechaarpornkul, et al.
OBJECTIVE: To determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement. METHODS: 367 primary knee osteoarthritis patients with a pain score of 5 or higher were randomized to receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks. The main outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores. Adverse events (AEs) were also recorded. RESULTS: 185 and 182 patients were randomly assigned into C. domestica extracts and ibuprofen groups, respectively. The baseline characteristics were no different between groups. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared with the baseline in both groups. After using the noninferiority test, the mean difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at week 4 adjusted by values at week 0 of C. domestica extracts were noninferior to those for the ibuprofen group (P=0.010, P=0.018, and P=0.010, respectively), except for the WOMAC stiffness subscale, which showed a trend toward significance (P=0.060). The number of patients who developed AEs was no different between groups. However, the number of events of abdominal pain/discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group (P=0.046). Most subjects (96%-97%) were satisfied with the treatment, and two-thirds rated themselves as improved in a global assessment. CONCLUSION: C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. The side effect profile was similar but with fewer gastrointestinal AE reports in the C. domestica extracts group.
14Clinical studies with curcumin.PubMed
Chih-Hung Hsu, Ann-Lii Cheng
Curcumin has long been expected to be a therapeutic or preventive agent for several major human diseases because of its antioxidative, anti-inflammatory, and anticancerous effects. In phase I clinical studies, curcumin with doses up to 3600-8000 mg daily for 4 months did not result in discernible toxicities except mild nausea and diarrhea. The pharmacokinetic studies of curcumin indicated in general a low bioavailability of curcumin following oral application. Nevertheless, the pharmacologically active concentration of curcumin could be achieved in colorectal tissue in patients taking curcumin orally and might also be achievable in tissues such as skin and oral mucosa, which are directly exposed to the drugs applied locally or topically. The effect of curcumin was studied in patients with rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers. Although the preliminary results did support the efficacy of curcumin in these diseases, the data to date are all preliminary and not conclusive. It is imperative that well-designed clinical trials, supported by better formulations of curcumin or novel routes of administration, be conducted in the near future.
15Obstacles against the Marketing of Curcumin as a Drug.PubMed
Kambiz Hassanzadeh, Lucia Buccarello, Jessica Dragotto, et al.
Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb , has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.
16Curcumin Formulations and Trials: What's New in Neurological Diseases.PubMed
Stella Gagliardi, Carlo Morasso, Polychronis Stivaktakis, et al.
Curcumin's pharmacological properties and its possible benefits for neurological diseases and dementia have been much debated. In vitro experiments show that curcumin modulates several key physiological pathways of importance for neurology. However, in vivo studies have not always matched expectations. Thus, improved formulations of curcumin are emerging as powerful tools in overcoming the bioavailability and stability limitations of curcumin. New studies in animal models and recent double-blinded, placebo-controlled clinical trials using some of these new formulations are finally beginning to show that curcumin could be used for the treatment of cognitive decline. Ultimately, this work could ease the burden caused by a group of diseases that are becoming a global emergency because of the unprecedented growth in the number of people aged 65 and over worldwide. In this review, we discuss curcumin's main mechanisms of action and also data from in vivo experiments on the effects of curcumin on cognitive decline.
17Implementing Curcumin in Translational Oncology Research.PubMed
Koraljka Gall Trošelj, Ivana Samaržija, Marko Tomljanović, et al.
Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status of publicly available data on curcumin clinical trials and a detailed presentation of results obtained so far with some curcumin formulations. Phenomena related to the observed effects of curcumin shown in clinical trials are presented, and its modifying effect on gut microbiota and metabolic reprogramming is discussed. Based on available data, there is a strong indication that curcumin and its metabolites present molecules that do not necessarily need to be abundant in order to act locally and benefit systemically. Future clinical studies should be designed in a way that will take that fact into consideration.
18Polyphenol Intervention Ameliorates Non-Alcoholic Fatty Liver Disease: An Updated Comprehensive Systematic Review.PubMed
Yazan Ranneh, Alaa S Bedir, Abdelghafar M Abu-Elsaoud, et al.
Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a challenging metabolic disorder with a strong emphasis on its prevention and management. Polyphenols, a group of naturally occurring plant compounds, have been associated with a decreased risk of various metabolic disorders related to NAFLD. The current systematic review aims to critically assess evidence about the ameliorative effect of polyphenol supplementation on NAFLD patients. A PRISMA systematic search appraisal was conducted in PubMed, Scopus, Web of Science Core Collection, and all relevant studies published prior to April 2024 and met the inclusion criteria were included. Twenty-nine randomized clinical trials (RCTs) comprised 1840 NAFLD patients. The studies primarily examined eleven phenolic compounds, including turmeric, curcumin, resveratrol, genistein, catechin, green tea extract, hesperidin, and silymarin. Turmeric and curcumin decreased liver enzymes, inflammatory cytokines, lipid profile, insulin resistance, and NAFLD score, while resveratrol did not present consistent results across all the studies. Most studies on silymarin showed a reduction in liver enzymes and lipid profile; however, no changes were observed in inflammatory cytokine levels. The dietary supplementation of hesperidin and naringenin or green tea extract caused improvements in liver enzyme, lipid profile, and inflammatory cytokine, while genistein supplementation did not modulate blood lipid profile. In conclusion, dietary supplementation of polyphenols could potentially prevent and ameliorate NAFLD. Still, the inconsistent results across the included RCTs require further clinical research to establish optimal dosage and duration.
19A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.PubMed
Kednapa Thavorn, Dianna Wolfe, Lena Faust, et al.
Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.
20Is curcumin bioavailability a problem in humans: lessons from clinical trials.PubMed
Ajaikumar B Kunnumakkara, Choudhary Harsha, Kishore Banik, et al.
: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principal component of turmeric is curcumin and its efficacy has been advocated in various and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem. : This article discusses over 200 clinical studies with curcumin that have demonstrated the pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies. : The therapeutic potential of curcumin, as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailability in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin, in combination with other compounds or as formulations, has shown enhanced bioavailability. Hence, bioavailability is not a problem in the curcumin-mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases.