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Chronic muscle and joint pain affect many people. However, current treatment options harbor a considerable risk of adverse drug reactions, which is why the search for other treatment alternatives is constantly expanding. As a result, research is also focusing on plant-based products. These include devil's claw, a medicinal plant from the sesame family, which is native to the African continent and is used there as a traditional remedy. In this study, 16 different criteria were selected for a critical analysis of devil's claw products, which included aspects such as drug-drug interactions, adverse drug reactions, and recommended daily dose, and 88 products were analyzed with the help of these criteria. Furthermore, products classified as food supplements, dietary supplements, and herbal medicinal products were compared with each other. Our goal was to analyze how consumers are informed, with a focus on consumer safety. The primary objective was not to analyze the actual ingredients of the products or to compare them based on their composition. The results almost invariably show the pharmaceutical reliability of herbal medicinal products. In contrast, products marketed as food supplements and dietary supplements have questionable reliability, as most products in these categories allow manufacturers more freedom and impose fewer controls and requirements. Devil's claw products labeled as food or dietary supplement show significant gaps in consumer information compared to herbal medicinal products. Product naming and packaging are often suggestive, potentially misleading consumers. Our study shows that food supplements and dietary supplements are clearly pursuing financial interests, and that consumer protection is often neglected in the process. The study analysis also revealed a limited number of clinical studies, no long-term studies, and poor methodological quality, undermining their reliability. © 2025. The Author(s).

BACKGROUND: In recent decades, complementary and alternative medicine (CAM) has become very popular in the treatment of several chronic diseases. Natural products as one of the CAM modalities offer potential opportunities to discover lead compounds for novel drug development. The use of CAM or natural products in the prevention of neurodegenerative diseases is comparatively a newer area. METHOD: A structured online literature search for peer-reviewed research articles was conducted on the PubMed, Europe PMC, Medline and Google Scholar portals, using phrases: natural products for neurologic disorders, phytomedicine for neurodegenerative diseases, natural therapeutics for neurological symptopms etc. Results: The retrieved data showed the natural therapeutics with anti-oxidative and anti-inflammatory salutations evidently plays a crucial role in protecting neurons. Of these, the most promising are caffeine, trigonelline, shogaol, curcumin, resveratrol, baicalein, wogonin, ginsenosides, tanshinones, withanolides, picrosides, parthenolide, cannabinoids, Devil's claw and white willow bark, including Chinese formulations Renshen Shouwu and Shengmai San. Though several herbs and their active ingredients have been studied in laboratory and clinical settings, only a few have been investigated for their molecular mechanisms of action. Notably, despite the promising and safe therapeutic benefits of CAM/herbal medicines, there exists a possible risk when combining them with prescription drugs. As a result, many drugs have shown changes in blood pressure, hepatotoxicity, seizures etc. when combined with certain herbs. CONCLUSION: Certainly, extensive work is needed to make sure that patients should take a regimen of protective and restorative therapy under an experienced healthcare professional. This article updates on the current knowledge of promising natural products used in neurological disorders.

PURPOSE: In recent years, a number of natural medicines have been reported to have inductive or inhibitive effects on the activity of drug metabolizing enzymes, upon co-administration with prescribed medicines. However, information regarding natural medicine-drug interactions that influence drug metabolism is limited owing to the lack of efficient screening method for such interactions. Therefore, to understand whether P450 activity is affected by natural medicine in small intestines, we have established frozen recombinant P450-expressing cells infected with human CYP3A4 expressing adenovirus (Ad-CYP3A4) to evaluate the effect of natural medicines on CYP3A4 activity. METHODS: Ad-CYP3A4 cells were created by infecting HepG2 cells with Ad-CYP3A4 at 10 multiplicity of infection (MOI) and these cells were stored using cryopreservation medium (fAd-CYP3A4 cells) to obtain long-term consistent data and stable supplies of cells expressing a constant level of CYP3A4 activity. RESULTS: The CYP3A4 activity in fAd-CYP3A4 cells remained unaffected at the end of each frozen period (0, 1, 2, and 6 months). Inhibitory effect on CYP3A4 activity by typical inhibitors (ketoconazole, hyperforin) and natural medicines (Cat's Claw, Devil's Claw, Feverfew, Peppermint Oil, Red Clover, and Siberian Eleuthero) were evaluated. The inhibitors had nearly equal IC50 values in fAd-CYP3A4 cells, Ad-CYP3A4 cells and recombinant CYP3A4 microsomes. Cat's Claw, Peppermint Oil and Siberian Eleuthero inhibited CYP3A4 activity more potently than 0.1 μM ketoconazole in fAd-CYP3A4 cells. CONCLUSIONS: In the present study, we have successfully developed a highly reproducible system to evaluate CYP3A4 inhibition in small intestines by natural medicines.

OBJECTIVES: Potential interactions between herbal medicinal products and the cytochrome (CYP) P450 system are an important safety concern. We set out to develop a screening panel for assessing such interactions and use it to evaluate the interaction potential of devil's claw. METHODS: The panel consisted of luminescence-based inhibition assays for CYP1A2, 2C9, 2C19, 2D6 and 3A4, and a reporter gene (luciferase) assay for pregnane X receptor (PXR) activation and CYP3A4 induction. Caftaric acid and chlorogenic acid, two compounds with strong fluorescence quenching properties, were used to demonstrate the assay's resistance to interference. We tested 10 commercial devil's claw preparations as well as harpagoside and harpagide, two important constituents of devil's claw. KEY FINDINGS: Five preparations were found to weakly inhibit CYP3A4 (IC50 124.2-327.6 µg/ml) and five were found to weakly activate PXR (EC50 10.21-169.3 µg/ml). Harpagoside and harpagide did not inhibit CYP3A4. In agreement with published data, bergamottin, a natural product known to interact with CYP3A4, was shown to inhibit CYP3A4 with an IC50 of 13.63 µm and activate PXR with an EC50 of 6.7 µm. CONCLUSIONS: Devil's claw preparations are unlikely to have a clinically relevant effect on CYP function. The assay panel proved effective in screening devil's claw preparations, demonstrating its suitability for use with plant extracts. It showed superior sensitivity and resistance to interference. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Devil's Claw (Harpagophytum procumbens) a plant native to Southern Africa, has historically been used in traditional medicine to treat a wide range of diseases and currently is widely employed as anti-inflammatory and pain-relieving natural remedy in Europe and other parts of the world. AIM OF THE STUDY: Little is known about possible herb-drug interactions arising from effects of Devil's Claw on the major drug metabolizing enzymes or transporters. This study evaluated in vitro the effects of Devil's Claw on the multidrug transporter ABCB1/P-glycoprotein. MATERIALS AND METHODS: The effects of three commercially available Devil's Claw preparations and that of pure harpagoside were studied in the human kidney (HK-2) proximal tubule cell line, constitutively expressing ABCB1/P-glycoprotein (P-gp). Pgp activity and expression were tested by the calcein-AM test and by Western blotting, respectively. RESULTS: Commercial preparations inhibited P-gp activity, even if to a different extent, while pure harpagoside was almost ineffective. In cells cultured for three days in the presence of Devil's Claw preparations or pure harpagoside, a dose-dependent P-gp upregulation was found. CONCLUSIONS: Our results demonstrate for the first time that Devil's Claw may interact with the multidrug transporter ABCB1/P-gp, the effect not appearing strictly related to the harpagoside relative content. Modulation of both P-gp activity and P-gp expression by Devil's Claw raise the possibility of herb-drug interactions, to be further explored in depth.

55. Altern Med Rev. 2008 Sep;13(3):248-52. Harpagophytum procumbens (devil's claw). Monograph. [No authors listed]

Harpagophytum procumbens, known as devil's claw, has been used traditionally for the treatment of pain, fevers, and dyspepsia. Recently, it has become popular for the treatment of rheumatoid and osteoarthritis. Studies have yet to establish a clear mechanism of action; however, current research is focusing on pro-inflammatory mediators as well as on potential antioxidant characteristics.

Comment in Int J Cardiol. 2006 Jun 7;110(1):93. doi: 10.1016/j.ijcard.2005.02.057. Use of herbal medicines among patients under cardiovascular pharmacotherapy is widespread. In this paper, we have reviewed the literature to determine the possible interactions between herbal medicines and cardiovascular drugs. The Medline database was searched for clinical articles published between January 1996 and February 2003. Forty-three case reports and eight clinical trials were identified. Warfarin was the most common cardiovascular drug involved. It was found to interact with boldo, curbicin, fenugreek, garlic, danshen, devil's claw, don quai, ginkgo, papaya, lycium, mango, PC-SPES (resulting in over-anticoagulation) and with ginseng, green tea, soy and St. John's wort (causing decreased anticoagulant effect). Gum guar, St. John's wort, Siberian ginseng and wheat bran were found to decrease plasma digoxin concentration; aspirin interactions include spontaneous hyphema when associated with ginkgo and increased bioavailability if combined with tamarind. Decreased plasma concentration of simvastatin or lovastatin was observed after co-administration with St. John's wort and wheat bran, respectively. Other adverse events include hypertension after co-administration of ginkgo and a diuretic thiazide, hypokalemia after liquorice and antihypertensives and anticoagulation after phenprocoumon and St. John's wort. Interaction between herbal medicine and cardiovascular drugs is a potentially important safety issue. Patients taking anticoagulants are at the highest risk.

Potential and documented interactions between alternative therapy agents and warfarin are discussed. An estimated one third of adults in the United States use alternative therapies, including herbs. A major safety concern is potential interactions of alternative medicine products with prescription medications. This issue is especially important with respect to drugs with narrow therapeutic indexes, such as warfarin. Herbal products that may potentially increase the risk of bleeding or potentiate the effects of warfarin therapy include angelica root, arnica flower, anise, asafoetida, bogbean, borage seed oil, bromelain, capsicum, celery, chamomile, clove, fenugreek, feverfew, garlic, ginger ginkgo, horse chestnut, licorice root, lovage root, meadowsweet, onion, parsley, passionflower herb, poplar, quassia, red clover, rue, sweet clover, turmeric, and willow bark. Products that have been associated with documented reports of potential interactions with warfarin include coenzyme Q10, danshen, devil's claw, dong quai, ginseng, green tea, papain, and vitamin E. Interpretation of the available information on herb-warfarin interactions is difficult because nearly all of it is based on in vitro data, animal studies, or individual case reports. More study is needed to confirm and assess the clinical significance of these potential interactions. There is evidence that a wide range of alternative therapy products have the potential to interact with warfarin. Pharmacists and other health care professionals should question all patients about use of alternative therapies and report documented interactions to FDA's MedWatch program.

Osteoarthritis (OA) is a progressive degenerative joint disease. It basically impairs the structural integrity of articulate cartilage and imbalances the catabolic and anabolic signals in the joint. A degenerative disease is characterized by swelling, pain, and joint stiffness. The treatment and management of osteoarthritis are based on analgesic and anti-inflammatory agents, whereas the exact cause of OA is not known yet. The negative effects of synthetic medications have led to a daily rise in the usage of nutraceuticals and dietary supplements. Clinicians are aware of these treatments, and they also recommend nutraceuticals in addition to the currently preferred therapy. Many in-vitro and in-vivo experiments have been performed in past years to evaluate the function of these on osteoarthritis. The collection of articles was published on search engines like PubMed, Scopus, Google Scholar, ResearchGate, and ScienceDirect. The evaluation covers every potential nutraceutical utilized in osteoarthritis, together with its supporting data and mode of action. The present review discusses nutraceuticals, including devil's claw, vitamin D, boswellic acid, capsaicin, ginger, curcumin, krill oil, ginger, and avocado/soybean unsaponifiable.

STUDY DESIGN: Systematic review of randomized controlled trials (RCTs). OBJECTIVES: To determine the effectiveness of herbal medicine for nonspecific low back pain (LBP). SUMMARY OF BACKGROUND DATA: Many people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. METHODS: We searched numerous electronic databases up to September 2014; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. We included RCTs examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic nonspecific LBP. The interventions were herbal medicines that we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared with assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. RESULTS: Fourteen RCTs (2050 participants) were included. Capsicum frutescens (cayenne) reduces pain more than placebo. Although Harpagophytum procumbens (devil's claw), Salix alba (white willow bark), Symphytum officinale L. (comfrey), Solidago chilensis (Brazilian arnica), and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. No significant adverse events were noted within the included trials. CONCLUSIONS: Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions. LEVEL OF EVIDENCE: N/A.

BACKGROUND: Low-back pain (LBP) is a common condition and imposes a substantial economic burden upon people living in industrialized societies. A large proportion of people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. OBJECTIVES: To determine the effectiveness of herbal medicine for non-specific LBP. SEARCH METHODS: We searched the following electronic databases up to September 2014: MEDLINE, EMBASE, CENTRAL, CINAHL, Clinical Trials.gov, World Health Organization International Clinical Trials Registry Portal and PubMed; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. SELECTION CRITERIA: We included randomized controlled trials (RCTs) examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic non-specific LBP. The interventions were herbal medicines which we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. DATA COLLECTION AND ANALYSIS: A library scientist with the Cochrane Back Review Group conducted the database searches. One review author contacted content experts and acquired relevant citations. We downloaded full references and abstracts of the identified studies and retrieved a hard copy of each study for final inclusion decisions. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared to assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. MAIN RESULTS: We included 14 RCTs (2050 participants) in this review. One trial on Solidago chilensis M. (Brazilian arnica) (20 participants) found very low quality evidence of reduction in perception of pain and improved flexibility with application of Brazilian arnica-containing gel twice daily as compared to placebo gel. Capsicum frutescens cream or plaster probably produces more favourable results th

13. Phytother Res. 2009 Nov;23(11):1497-515. doi: 10.1002/ptr.3007. Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part I: Osteoarthritis. Cameron M(1), Gagnier JJ, Little CV, Parsons TJ, Blümle A, Chrubasik S. Author information: (1)School of Sport and Exe

STUDY DESIGN: A systematic review of randomized controlled trials. OBJECTIVES: To determine the effectiveness of herbal medicine compared with placebo, no intervention, or "standard/accepted/conventional treatments" for nonspecific low back pain. SUMMARY OF BACKGROUND DATA: Low back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients with chronic low back pain use complementary and alternative medicine (CAM) and/or visit CAM practitioners. Several herbal medicines have been purported for use in low back pain. METHODS: The following databases were searched: Medline (1966 to April 2003), Embase (1980 to April 2003), Cochrane Controlled Trials Register (Issue 1, 2003), and Cochrane Complementary Medicine (CM) field Trials Register. Additionally, reference lists in review articles, guidelines, and in the retrieved trials were checked. Randomized controlled trials (RCTs), using adults (>18 years of age) suffering from acute, subacute, or chronic nonspecific low back pain. Types of interventions included herbal medicines defined as a plant that is used for medicinal purposes in any form. Primary outcome measures were pain and function. Two reviewers (J.J.G. and M.W.T.) conducted electronic searches in all databases. One reviewer (J.J.G.) contacted content experts and acquired relevant citations. Authors, title, subject headings, publication type, and abstract of the isolated studies were downloaded or a hard copy was retrieved. Methodologic quality and clinical relevance were assessed separately by two individuals (J.J.G. and M.W.T.). Disagreements were resolved by consensus. RESULTS: Ten trials were included in this review. Two high-quality trials utilizing Harpagophytum procumbens (Devil's claw) found strong evidence for short-term improvements in pain and rescue medication for daily doses standardized to 50 mg or 100 mg harpagoside with another high-quality trial demonstrating relative equivalence to 12.5 mg per day of rofecoxib. Two moderate-quality trials utilizing Salix alba (White willow bark) found moderate evidence for short-term improvements in pain and rescue medication for daily doses sta

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interaction, adverse effects, toxicology, and dosing.

BACKGROUND: Low-back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients with chronic low-back pain use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in low-back pain. OBJECTIVES: To determine the effectiveness of herbal medicine for non-specific low-back pain. SEARCH STRATEGY: We searched the following electronic databases: Cochrane Complementary Medicine Field Trials Register (Issue 3, 2005), MEDLINE (1966 to July 2005), EMBASE (1980 to July 2005); checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this very specialized area. SELECTION CRITERIA: We included randomized controlled trials, examining adults (over 18 years of age) suffering from acute, sub-acute or chronic non-specific low-back pain. The interventions were herbal medicines, defined as plants that are used for medicinal purposes in any form. Primary outcome measures were pain and function. DATA COLLECTION AND ANALYSIS: Two authors (JJG & MVT) conducted the database searches. One author contacted content experts and acquired relevant citations. Full references and abstracts of the identified studies were downloaded. A hard copy was retrieved for final inclusion decisions. Methodological quality and clinical relevance were assessed separately by two individuals. Disagreements were resolved by consensus. MAIN RESULTS: Ten trials were included in this review. Two high quality trials examining the effects of Harpagophytum Procumbens (Devil's Claw) found strong evidence that daily doses standardized to 50 mg or 100 mg harpagoside were better than placebo for short-term improvements in pain and rescue medication. Another high quality trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx). Two trials examining the effects of Salix Alba (White Willow Bark) found moderate evidence that daily doses standardized to 120 mg or 240 mg salicin were better than placebo for short-term improvements in pain and rescue medication. An additional trial demonstrated

BACKGROUND: Ulcerative colitis is an autoimmune disease with an unfamiliar etiology, which caused by environmental, microbial, and genetic factors. Harpagophytum procumbens (H. procumbens, Devil's Claw), could be effective in the treatment of colitis due to its strong anti-inflammatory, antioxidant and restorative effects. Therefore, this research aimed to explore this property. METHODS: The hydroalcoholic extract of H. procumbens was prepared and partitioned into aqueous and ethyl acetate parts. Total phenols of extract and partitions were determined and three increasing doses of them (50, 100, and 200 mg/kg), dexamethasone (1 mg/kg), mesalazine (100 mg/kg) and normal saline (5 mL/kg) were examined in male Wistar rats as test, reference and control groups respectively. Colitis induction was conducted via rectal instillation of acetic acid and the treatments continued for five consecutive days. Finally, the colon tissues were evaluated for colitis biomarkers. RESULTS: Total phenols were equivalent to 5.19 ± 0.09, 2.12 ± 0.03 and 7.71 ± 0.01 gallic acid equivalent (mg)/g of dry extract, aqueous and ethyl acetate partitions, respectively. Greater doses of hydroalcoholic extract and aqueous (200 mg/kg) and ethyl acetate partition (50, 100 and 200 m

Erratum for Front Pharmacol. 2026 Jun 17;17:1839470. doi: 10.3389/fphar.2026.1839470. [This corrects the article DOI: 10.3389/fphar.2026.1839470.].

Harpagophytum procumbens (Burch.) DC., commonly known as devil's claw, is traditionally used in southern Africa for treating inflammatory conditions. Despite its widespread use, comprehensive toxicological and antioxidant evaluations using alternative invertebrate models remain limited. This study investigated the phytochemical composition, acute toxicity, repellent activity, antioxidant capacity, and effects on oxidative stress markers of H. procumbens dry extract (HpDE) using Nauphoeta cinerea as a model organism. HPLC analysis identified six major phenolic compounds: gallic acid, catechin, caffeic acid, rosmarinic acid, rutin, and quercetin. Survival assays using concentrations of 15.625, 31.25, 62.5, 125, and 250 mg/mL demonstrated 100% survival of N. cinerea

INTRODUCTION: Medicinal plants and their preparations are of great interest to many patients with rheumatic diseases. In 2023 the German Society for Rheumatology and Clinical Immunology (DGRh) Committee for Complementary Medicine and Nutrition (KHE) began reviewing the scientific literature on selected phytotherapeutic agents and herbal preparations and examining their potential applications in rheumatology. Following the publication of the initial results in 2025, the evaluation of 13 additional phytotherapeutic agents took place later that same year. METHODS: In an online meeting of the KHE Committee on 7 January 2025, a further list of phytotherap

Erratum in Front Pharmacol. 2026 Jul 28;17:1930236. doi: 10.3389/fphar.2026.1930236. Harpagophytum procumbens (HP), commonly known as Devil's Claw, is a traditional medicinal plant widely used for musculoskeletal pain and inflammatory conditions. Interest in HP has increased because long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may be limited by gastrointestinal, cardiovascular, and renal adverse effects. This structured narrative review summarizes current evidence regarding the pharmacological mechanisms, clinical efficacy, safety, pharmacokinetics, regulatory status, and comparative role of HP relative to NSAIDs. Preclinical studies suggest that HP and its constituents, particularly harpagoside, may modulate inflammatory pathways including cyclooxygenase-2, nuclear factor-κB, pro-inflammatory cytokines, and oxidative stress signaling. However, these mechanistic findings represent indirect evidence and should be interpreted cautiously in relation to clinical outcomes. Clinical studies, mainly in osteoarthritis and low back pain, suggest that selected HP preparations may provide symptomatic benefit in some patients. However, the clinical evidence base remains limited by small sample sizes, heterogeneous formulations, variable dosages, short follow-up durations, and a scarcity of high-quality head-to-head randomized trials against NSAIDs. In contrast, NSAIDs are supported by a substantially broader and higher-certainty evidence base for pain relief and functional improvement. Available safety data suggest that HP is generally well tolerated, although product quali

Osteoarthritis (OA) is a common musculoskeletal disorder in canines, characterized by discomfort, lameness, and reduced mobility. Because of the inconsistent efficacy of available treatments, and that a definitive resolution can be achieved only in a small number of cases, OA remains a major challenge in veterinary orthopedics. The current strategy is usually a multimodal approach involving systemic administration of anti-inflammatory drugs, intra-articular therapies, physiotherapy, dietary modifications, and nutraceuticals. The main goals are to slow progression, preserve joint function, and alleviate pain and inflammation. Although non-steroidal anti-inflammatory drugs (NSAIDs) are effective agents for controlling OA signs, their long-term use is associated with adverse effects. Therefore, in recent years, growing attention has been directed toward nutraceutical compounds. Thanks to their natural origin and safety, these products have shown promising results in reducing pain and inflammation in dogs with spontaneous osteoarthritis, representing a valuable alternative or complementary option. The aim of this study was to evaluate the efficacy of a nutraceutical formulation, mainly composed of fish oil, unsaponificable fraction from Avocado and Soy seeds, Turmeric extract, Devil's Claw, Boswellia, Salix alba extract, Piper nigrum, Haematococcus pluvialis, Magnesium salt of stearic acid, maltodextrin (Asudyn®), by comparing its short- and mid-term clinical, radiographic, and cytological outcomes

Harpagoside, a pharmacologically active iridoid glycoside from Harpagophytum procumbens (Devil's Claw), exhibits broad therapeutic properties including anti-inflammatory, antioxidant, analgesic, anticancer, and bone-protective effects. Preclinical studies demonstrate pathway modulation at concentrations of 10-50 μM, targeting NF-κB, AP-1, Nrf2/HO-1, PI3K/Akt, and MAPKs, with in vivo evidence for bone preservation, metabolic regulation, and neuroprotection. Clinical trials using standardized extracts (50-100 mg/day harpagoside or 2.6 g/day powdered root) have reported significant improvements in osteoarthritis and chronic low back pain, with fewer gastrointestinal adverse effects compared to NSAIDs. Unlike previous reviews, this article emphasizes the multi-pathway and systems pharmacology mechanisms of harpagoside, its prodrug-like behavior through biotransformation into active metabolites, and formulation strategies, such as nanoparticles, phospholipid complexes, and semi-synthetic derivatives, to overcome poor oral bioavailability. Current challenges include variability in phytochemical content, limited pharmacokinetic and safety data, and insufficient GLP-compliant long-term toxicity studies.

OBJECTIVE: Stroke is a highly prevalent and devastating condition affecting millions worldwide. The Devil's Claw (DCW) plant is a native African plant whose anti-inflammatory, antioxidant, and neuroprotective properties have been investigated. We postulated that DCW could protect the brain injury caused by cerebral ischemia. MATERIALS AND METHODS: The rats were randomly divided into four groups. The sham and control (Ctrl) groups received pretreatment with a distilled water vehicle. Doses of 200 and 400 mg/kg were selected for pretreatment with DCW. The filament or intravascular occlusion method was used for middle cerebral artery occlusion (MCAO). The Triphenyl tetrazolium chloride (TTC) staining method was used to investigate the infarct zone and penumbra volume. The neuroprotective effect of DCW was measured by hematoxylin staining. Movement performance was evaluated from neurological deficit score, rotarod performance, and open field tests. RESULTS: TTC staining showed that the DCW/400 group could maintain the penumbra's structure and reduce the infarct volume compared to the Ctrl group (p<0.001). Histological studies confirmed the neuroprotective properties of DCW at doses of 200 and 400 mg/kg compared to the Ctrl group (p<0.01 and p<0.0001, respectively). The results of behavioral

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition's complexities.

Osteoarthritis (OA) is an age-related degenerative joint disease with a gre

Microglial activation has been associated to the physiopathology of neurodegenerative diseases, such as schizophrenia, and can occur during inflammation and oxidative stress. Pharmacological treatment is associated with severe side effects, and studies for use of plant extracts may offer alternatives with lower toxicity. Harpagophytum procumbens (HP) is a plant known for its anti-inflammatory properties. In the present study, we characterized the ethyl acetate fraction of HP (EAF HP) by ESI-ToF-MS and investigated the effects EAF HP in a lipopolysaccharide (LPS) induced inflammation model on microglial cells (BV-2 lineage). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), DCFH-DA (2',7'-dichlorofluorescein diacetate) and cell cycle flow cytometer analysis were performed. In vivo was investigated the amphetamine-induced psychosis model through behavioral (locomotor and exploratory activities, stereotypies and working memory) and biochemical (DCFH-DA oxidation and protein thiols) parameters in cortex and striatum of mice. EAF HP reduced activatio

Harpagophytum procumbens subsp. procumbens (Burch.) DC. ex Meisn. (Sesame seed Family-Pedaliaceae) is a popular medicinal plant known as Devil's claw. It is predominantly distributed widely over southern Africa. Its impressive reputation is embedded in its traditional uses as an indigenous herbal plant for the treatment of menstrual problems, bitter tonic, inflammation febrifuge, syphilis or even loss of appetite. A number of bioactive compounds such as terpenoids, iridoid glycosides, glycosides, and acetylated phenolic compounds have been isolated. Harpagoside and harpagide, iridoid glycosides bioactive compounds have been reported in countless phytochemical studies as potential anti-inflammatory agents as well as pain relievers. In-depth studies have associated chronic inflammation with various diseases, such as Alzheimer's disease, obesity, rheumatoid arthritis, type 2 diabetes, cancer, and cardiovascular and pulmonary diseases. In addition, 60% of chronic disorder fatalities are due to chronic inflammatory diseases worldwide. Inflammation and pain-related disorders have attracted significant attention as leading causes of global health challenges. Articles published from 2011 to the present were obtained and reviewed in-depth to determine valuable data findings as well as knowledge gaps. Various globally recognized scientific search engines/databases including Scopus, PubMed, Google Scholar, Web of Science, and ScienceDirect were utilized to collect information and deliver evidence. Based on the literature results, there was a dramatic decrease in the number of studies conducted on the anti-inflammatory and analgesic activity of Devil's claw, thereby presenting a potential research gap. It is also evident that currently in vivo clinical stu

Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) are diseases of the gastrointestinal system involving genetic and environmental factors attributed to oxidative stress and inflammation. Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the important therapeutic strategies to keep the disease in remission. As there is no permanent cure for IBD except for chronic long-term treatment or surgery, it is therefore imperative to investigate plant-based agents that are receiving attention for their therapeutic benefits to overcome the debilitating clinical conditions of IBD. Lycopodium (LYCO), a plant of tropical and subtropical origin and known by numerous names such as ground pine, club moss, or devil's claw, has been popularly used for centuries in traditional medicine including Chinese and Indian medicines. In the present study, the effect of LYCO has been investigated in an acetic acid (AA)-induced colitis model in Wistar rats. LYCO was orally administered at the dose of 50 mg/kg/day either 3 days before or 30 min after the induction of IBD and continued for 7 days by intrarectal administration of AA. The changes in body weight and macroscopic and microscopic analysis of the colon of rats of different experimental groups were observed on days 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), reduced glutathione (GSH), and malondialdehyde (MDA) were measured. AA caused a significant reduction in body weight and increased macroscopic and microscopic ulcer score

The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the present study, the involvement of Harpagophytum procumbens root extract, a common ingredient of nutraceuticals used to treat joint disorders, in CB2 modulation has been evaluated. Moreover, to clarify the effects of the pure single components, the bioactive constituent, harpagoside, and the main volatile compounds were studied alone or in a reconstituted mixture. Human fibroblast-like synoviocytes, extracted by joints of patients, who underwent a total knee replacement, were treated with an H. procumbens root extract dissolved in DMSO (HPEDMSO). The effectiveness of HPEDMSO to affect CB2 pathways was studied by analyzing the modulation of cAMP, the activation of PKA and ERK MAP kinase, and the modulation of MMP-13 production. HPEDMSO was able to inhibit the cAMP production and MAP kinase activation and to down-regulate the MMP-13 production. Pure compounds were

Psoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil's claw (Harpagophytum procumbens (Burch.) DC. ex Meisn.) tubers extract has been used both systemically and topically for treatment of chronic inflammatory diseases such as arthritis, osteoporosis, inflammatory bowel disease, among others. However, its potential mechanisms of action against psoriasis remains poorly investigated. The human keratinocyte HaCaT cell line is a well-accepted in vitro model system for inflammatory skin disorders such as psoriasis. The present study involved an exploration of the effect of biotechnologically produced H. procumbens (HP) cell suspension extract and pure phenylethanoid glycosides verbascoside (VER) and leucosceptoside A (LEU) in interferon (IFN)-γ/interleukin (IL)-17A/IL-22-stimulated HaCaT cells as a model of psoriasis-like inflammation. Changes in key inflammatory signaling pathways related to psoriasis development were detected by reverse transcription polymerase chain reaction and western blotting. Treatment with LEU, but not VER and HP extract improved psoriasis-related inflammation via suppression of the PI3K/AKT signaling in IFN-γ/IL-17A/IL-22-stimulated HaCaT cell

Devil's claw is the vernacular name for a genus of medicinal plants that occur in the Kalahari Desert and Namibia Steppes. The genus comprises two distinct species: Harpagophytum procumbens and H. zeyheri. Although the European pharmacopeia considers the species interchangeable, recent studies have demonstrated that H. procumbens and H. zeyheri are chemically distinct and should not be treated as the same species. Further, the sale of H. zeyheri as an herbal supplement is not legal in the United States. Four markers were tested for their ability to distinguish H. procumbens from H. zeyheri: rbcL, matK, nrITS2, and psbA-trnH. Of these, only psbA-trnH was successful. A novel DNA mini-barcode assay that produces a 178-base amplicon in Harpagophytum (specificity = 1.00 [95% confidence interval = 0.80-1.00]; sensitivity = 1.00 [95% confidence interval = 0.75-1.00]) was used to estimate mislabeling frequency in a sample of 23 devil's claw supplements purchased in the United States. PCR amplification failed in 13% of cases. Among the 20 fully-analyzable supplements: H. procumbens was not detected in 75%; 25% contained both H. procumbens and H. zeyheri; none contained only H. procumbens. We recommend this novel mini-barcode region as a standard method of quality control in the manufacture of devil's claw supplements.

Devil's claw (Harpagophytum spp., Pedaliaceae) is one of the best-documented phytomedicines. Its mode of action is largely elucidated, and its efficacy and excellent safety profile have been demonstrated in a long list of clinical investigations. The author conducted a bibliographic review which not only included peer-reviewed papers published in scientific journals but also a vast amount of grey literature, such as theses and reports initiated by governmental as well as non-governmental organizations, thus allowing for a more holistic presentation of the available evidence. Close to 700 sources published over the course of two centuries were identified, confirmed, and cataloged. The purpose of the review is three-fold: to trace the historical milestones in devil's claw becoming a modern herbal medicine, to point out gaps in the seemingly all-encompassing body of research, and to provide the reader with a reliable and comprehensive bibliography. The review covers aspects of ethnobotany, taxonomy, history of product development and commercialization, chemistry, pharmacology, toxicology, as well as clinical efficacy and safety. It is concluded that three areas stand out in need of further investigation. The taxonomical assessment of the genus is outdated and lacking. A revision is needed to account for intra- and inter-specific, geographical, and chemo-taxonomical variation, including variation in composition. Further research is needed to conclusively elucidate the active compound(s). Confounded by early substitution, intermixture, and blending, it has yet to be demonstrated beyond a reasonable doubt that both (or all) Harpagophytum spp. are equally (and interchangeably) safe and efficacious in clinical practice.

There is a need for inexpensive and reliable means to determine the modulation of cutaneous inflammation. The method outlined in this article draws together a number of scientific techniques and makes use of generally unwanted biological tissues as a means of determining skin inflammation ex vivo, and focuses on probing aspects of the arachidonic acid inflammation pathway. Freshly excised skin contains elevated levels of short-lived inducible cyclooxygenase-2 (COX-2) and, under viable conditions, COX-2 and its eicosanoid products will continue to be produced until tissue necrosis, providing a window of time in which relative levels can be probed to determine exacerbation due to an upregulating factor or downregulation due the presence of an agent exerting anti-inflammatory activity. Ex vivo porcine skin, mounted in Franz diffusion cells, is dosed topically with the xenobiotic challenge and then techniques such as Western blotting and immunohistochemistry can then be used to probe relative COX-2 levels on a semi-quantitative or qualitative level. Enzyme-linked immunosorbent assay or LCMS can be used to determine relative prostaglandin E-2 (PGE-2) levels. Thus far, the technique has been used to examine the effects of topically applied anti-inflammatories (betamethasone, ibuprofen, ketoprofen and methotrexate), natural products (fish oil, Devil's claw extract and pomegranate rind extract) and drug delivery vehicle (polyNIPAM nanogels). Topically applied xenobiotics that modulate factors such as COX-2 and PGE-2 must penetrate the intact skin, and this provides direct evidence of overcoming the "barrier function" of the stratum corneum in order to target the viable epidermis in sufficient levels to be able to elicit such effects. This system has particular potential as a pre-clinical screening tool for those

Worldwide, medicinal plants and herbal medicines are widely consumed. The aim of this study was to determine macro- (Ca, K, Mg, Na, and P) and microelements (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se, Si, Sn, Sr, V, and Zn) in medicinal plants and herbal medicines: "globe artichoke" - Cynara scolymus L., "devil's claw" - Harpagophytum procumbens D.C., and "espinheira santa" - Maytenus ilifolia (Mart) ex Reiss. Concentrations of 24 (essential and toxic potentially) elements in samples from Brazil were determined using a sequential optical emission spectrometer with inductively coupled plasma optical emission spectrometry (ICP OES) after acid digestion, assisted by microwave radiation. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to carry out an exploratory analysis of samples. The elements were quantified (in μg/g): Al (20.24-1261.64), Ba (18.90-63.18), Ca (2877.6-19,957.40), Cr (0.28-1.38), Cu (4.16-21.99), Fe (8.54-627.49), K (1786.12-32,297.19), Mg (505.82-6174.52), Mn (0.40-205.64), Na (1717.23-18,596.45), Ni (< LoQ-0.99), P (35.12-2899.91), Se (1.52-3.71), Sn (1.53-12.43), Sr (52.33-84.31)

Over 200 million people are exposed to arsenic worldwide in their daily lives. Arsenic is a toxic ubiquitous metalloid distributed in the ground water. From the last few decades it is obtaining considerable attention for its severe neurotoxic properties. In this study the neuroprotective efficacy of devil's claw (DCW), a potent antioxidant has been investigated against arsenic induced neurotoxicity in female rats. Neurotoxicity was established by oral administration of 13 mg/kg sodium arsenite. The animals were divided into five groups (n = 6) including normal control, disease/arsenic control, standard treatment (Apocynin, 10 mg/kg), DCW treatment I (DCW, 200 mg/kg) and DCW treatment II (DCW, 400 mg/kg). Exploratory, anxiety and motor coordination related behavior of the animals was assessed using hole-board, forced swimming, beam walk and elevated plus maze tests. Findings revealed that DCW treatment ameliorated anxiety and motor in-coordination in the rats compared to the arsenic control group. In addition, arsenic induced a significant oxidative stress in arsenic only treated group, whereas co-administration with DCW the oxidative stress was reduced prominently. Arsenic control group produced gliosis and nuclear pyknosis of the brain cells which were prominently suppressed with the treatment of DCW for 21 days. The activity of DCW was in correlation with the concentration of harpagoside in the serum estimated by the HPLC method, supports that harpagoside was the active constituent responsible for neuroprotective effect. Further findings are required to understand the molecular mechanisms involved in neuroprotective effec

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

Devil's Claw is a traditional medicine that has been long used a wide range of health conditions, including indigestion, fever, allergic reactions, and rheumatism. The main compounds are iridoid glycosides, including harpagoside, harpagide, and procumbide. However, harpagoside is the most responsible for therapeutic activity, and its content is used as reference standard. Here, we analyzed and summarized preclinical and clinical studies focusing on therapeutic efficacy of devil's claw preparations in pathological conditions in which inflammation plays a key causative role. Publisher: Devil's claw (Harpagophytum procumbens) is an herbaceous plant, which can be found in the arid steppes of South Africa, particularly in the Kalahari Desert. As traditional medicine, devil's claw has been long used in the forms of infusions, decoctions, tinctures, powders, and extracts. The main compounds of devil's claw are iridoid glycosides, such as harpagoside, harpagide, and procumbide, which are present in the plant tubers. Additionally, chemical constituents such as sugars (mainly the tetrasaccharide stachyose), triterpenoids (oleanolic and ursolic acid), phytosterols (primarily β-sitosterol), aromatic acids (caffeic, cinnamic, and chlorogenic acids), and flavonoids (luteolin and kaempferol) can be found in the plant. In order to investigate the applicative potential of devil's claw as therapeutic agent, we performed a review by focusing on its potential role in managing inflammation- and oxidative stre

Preparations from the dried tubers of Harpagophytum procumbens (Burch.) DC ex Meisn, commonly known as devil's claw, are mainly used in modern medicine to relieve joint pain and inflammation in patients suffering from rheumatic and arthritic disorders. This paper describes for the first time the chemical profile of a commercial spagyric tincture (named 019) prepared from the roots of the plant. For comparison purposes, a commercial not-spagyric devil's claw tincture (NST) was also analyzed. Chemical investigation of the content of specialized metabolites in the three samples indicated that harpagoside was the main compound, followed by the two isomers acteoside and isoacteoside. Compositional consistence over time was obtained by the chemical fingerprinting of another spagyric tincture (named 014) from the same producer that was already expired according to the recommendation on the label of the product. The two spagyric preparations did not show significant compositional differences as revealed by HPLC and MS analyses, except for a decrease in harpagide content in the expired 014 tincture. Moreover, their antioxidant capacities as assessed by 2,2'-di-phenyl-1-picrylhydrazyl (DPPH) and 2.2'-azin-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods resulted in very similar IC50 values. The expired 014 tincture showed instead a lower IC50 value compared to the 019 and NST tinctures with the ferric reducing antioxidant potential (FRAP) assay, indicating a higher ferric-reducing antioxidant ability. Overall, these results indicated that the two preparations could generally maintain good stability and