A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Treatment of rheumatic musculoskeletal disorders.

Non-medicinal therapies with water, salts, exercise, massage, supportive devices, and electricity have been used for centuries and continue to be of benefit for some people with musculoskeletal disorders. Historical texts refer to the two electuaries mithridatium and theriaca as early therapeutic attempts of man to provide relief of musculoskeletal symptoms and attempt disease cures. For over 200 years, morphine-derived products have been used for musculoskeletal pain. The development of acetyl salicylic acid was a major breakthrough in joint pain management. This was followed by the introduction of nonsteroidal anti-inflammatory agents, paracetamol, and the use of corticosteroids. The gold-based compounds were the initial disease-modifying drugs and have been followed by the highly successful biologics agents. The basic objectives of musculoskeletal pain management include: reduction or elimination of joint pain; improvement or restoration of joint function and mobility; improvement of muscle strength to protect cartilage, ligaments, and joint capsule; prevention and reduction of damage to joint cartilage and supporting structures.

Safety of esthetic procedures in rheumatic patients: single-center survey of patients.

The popularity of esthetic medicine is growing every year, also among patients with autoimmune inflammatory rheumatic diseases (AIRD). The objective of this study was to evaluate the safety of esthetic medicine (AM) procedures in patients with AIRD. A semi-structured, anonymous questionnaire regarding rheumatic and concomitant diseases and AM procedures was distributed among adult patients hospitalized in the rheumatology department or attending outpatient clinic in the National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw. The main outcome was the occurrence of an adverse event. A number of 512 patients took part in the survey and 15 were excluded (AM procedure preceded the diagnosis of AIRD). The study group consisted of 497 patients, of whom 47 had undergone AM procedures. The procedures performed included: tattooing (22 patients), piercing (16 patients), hyaluronic acid (7 patients), botulinum toxin (5 patients) injections, laser procedures (6 patients), plastic surgery (4 patients), mesotherapy (3 patients) and others. The vast majority of patients had these performed during remission or low disease activity. 70.2% of patients received treatment with disease-modifying antirheumatic drugs (DMARDs) during the AM procedure, with TNF-alfa inhibitors being the most common (63.6%). Adverse events occurred in 15% of patients. All were mild and transient site reactions. Most patients would like to repeat the AM procedure in the future. The use of esthetic medicine procedures in patients with AIRD, including those treated with biologic DMARDs, was associated with a risk of mild site reactions. Most of the patients expressed satisfaction with the results of the AM procedure.

Anemia and iron deficiency in pregnant women with rheumatic diseases.

INTRODUCTION: Anemia and iron deficiency are the most common pathologies in pregnancy and associated with adverse pregnancy outcome. As patients with rheumatic diseases are also at high risk for anemia, we aimed to investigate the frequency of anemia and iron deficiency during pregnancy in this group and whether anemia is a risk factor for adverse maternal or child outcome. METHODS: We analyzed 368 pregnancies from a German registry for pregnancies in patients with rheumatic diseases (TURIRE) from 2014-2022. Anemia and iron deficiency were defined according to the World Health Organization. Main outcome measures were prevalence of anemia, iron deficiency, and adverse outcomes. RESULTS: From the 368 patients 61% were diagnosed with a connective tissue disease, 16% with rheumatoid arthritis or juvenile idiopathic arthritis, 14% with spondyloarthritis, 3% with vasculitis and 7% with other. Prevalence of anemia/iron deficiency was 18%/28% in the first, 27%/51% in the second and 33%/62% in the third trimester. Low hemoglobin levels (OR 0.52) or iron deficiency (OR 0.86) had a negative impact on child outcome. However, lower hemoglobin levels were associated with a lower risk for maternal complications (OR 1.47). CONCLUSION: Prevalence of anemia and iron deficiency is high in pregnant women with rheumatic diseases. Compared to previously published cohorts of the general population from different countries, the prevalence of anemia and iron deficiency is distinctly higher. Furthermore, patients with rheumatic diseases already start with impaired iron storage and/or hemoglobin levels. Thus, iron supplementation should be initiated early on in this vulnerable in this patient group.

Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?

Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: "vitamin D" combined with the terms "juvenile idiopathic arthritis", "juvenile systemic scleroderma", "juvenile systemic lupus erythematosus", "juvenile inflammatory myopathies", "Behcet disease", "periodic fever syndromes" and "juvenile rheumatic diseases". Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose-response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.

Rheumatological patients' knowledge of, beliefs about, and practices in using phytotherapy: an exploratory study.

Phytotherapy has emerged as a new concept and has quickly and widely spread in recent years. Studies on phytopharmaceuticals in rheumatology practice are very limited. In this study, we aimed to examine the knowledge of, beliefs about, and practices of using phytotherapy in patients who use biologics due to rheumatological disease. In the first part of the questionnaire, there are 11 questions, including the demographic data of the person, and in the second part, there are 17 questions that aim to learn the level of knowledge about phytotherapy and the use of phytopharmaceuticals. The questionnaire was administered face-to-face to patients with rheumatology using biological therapy who gave consent to participate. A total of 100 patients who were followed up with biological therapy were included in the final analysis. Approximately half of participants (48%) received any phytopharmaceuticals during their biologic treatment. Camellia sinensis (green tea) and Tilia platyphyllos were the most preferred phytopharmaceuticals. Gender, age, smoking, duration of disease, and duration of biologic treatment were not found to be associated with the use of phytopharmaceuticals. Of the 100 participants, 69% had information about phytotherapy, and the primary sources of information about phytotherapy were television and social media. Rheumatological diseases cause chronic pain, multiple drug use, and a decrease in quality of life, so the search for alternative treatment methods is frequent in these patients. Studies with a high level of evidence are necessary for healthcare professionals to inform their patients about this topic.

Beyond Seasoning-The Role of Herbs and Spices in Rheumatic Diseases.

Although we have witnessed remarkable progress in understanding the biological mechanisms that lead to the development of rheumatic diseases (RDs), remission is still not achieved in a substantial proportion of patients with the available pharmacological treatment. As a consequence, patients are increasingly looking for complementary adjuvant therapies, including dietary interventions. Herbs and spices have a long historical use, across various cultures worldwide, for both culinary and medicinal purposes. The interest in herbs and spices, beyond their seasoning properties, has dramatically grown in many immune-mediated diseases, including in RDs. Increasing evidence highlights their richness in bioactive molecules, such as sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, as well as their antioxidant, anti-inflammatory, antitumorigenic, and anticarcinogenic properties. Cinnamon, garlic, ginger, turmeric, and saffron are the most popular spices used in RDs and will be explored throughout this manuscript. With this paper, we intend to provide an updated review of the mechanisms whereby herbs and spices may be of interest in RDs, including through gut microbiota modulation, as well as summarize human studies investigating their effects in Rheumatoid Arthritis, Osteoarthritis, and Fibromyalgia.

Melatonin supplementation improves rheumatological disease activity: A systematic review.

BACKGROUND: Melatonin is a pineal hormone with a complex role. It is linked to sleep, inflammatory, oxidative, and immunological processes. AIM: To review the use of melatonin supplementation in rheumatological diseases. METHODS: A systematic search of PubMed, Embase, and Scielo databases was performed, looking for articles on Melatonin and rheumatic diseases published between 1966 and August 2022. RESULTS: Thirteen articles were identified: in fibromyalgia (n = 5 articles), rheumatoid arthritis (n = 2), systemic sclerosis (n = 1), systemic lupus erythematosus (n = 1) and osteoporosis/osteopenia (n = 3) and osteoarthritis (n = 1). There were positive results of melatonin administration in fibromyalgia, osteoarthritis, and osteoporosis/osteopenia but not in rheumatoid arthritis and lupus. The drug was well tolerated with mild side effects. CONCLUSION: This review shows the efficacy of Melatonin in some rheumatic diseases. However, new studies are needed to elucidate the real role of this treatment in rheumatology.

[Non-pharmacological management for inflammatory rheumatic diseases]. / Traitements non médicamenteux des rhumatismes inflammatoires chroniques.

Chronic inflammatory arthritis are conditioners with many drug treatments available. However, many patients still suffer from symptoms impairing their quality of life. It seems necessary to propose complementary therapies favoring patients' involvement in their management. We detail several axes: nutrition and micronutrition, physical activity, management of comorbidities such as obesity, smoking and periodontitis as well as physical therapies with cryotherapy and occupational therapy.

Les rhumatismes inflammatoires chroniques sont des maladies fréquentes avec de nombreux traitements médicamenteux à disposition. Toutefois, un nombre significatif de patients conservent des symptômes qui altèrent leur qualité de vie. Il paraît nécessaire de proposer des thérapies complémentaires adaptées à chaque patient en l'impliquant dans sa prise en charge. Nous détaillons ainsi plusieurs axes : la nutrition et la micronutrition, l'activité physique, la prise en charge des comorbidités telles que l'obésité, le tabagisme et la parodontite, ainsi que les thérapies physiques avec la cryothérapie et l'ergothérapie.

Perceived treatment satisfaction in patients with systemic rheumatic diseases treated with biologic therapies: results of a self-reported survey.

Biological agents are widely used for the management of systemic rheumatic diseases (SRDs) and their therapeutic implications have been expanded beyond inflammatory arthropathies to more complicated autoimmune disorders, such as systemic lupus erythematosus, vasculitis, and systemic sclerosis. The aim of this study was to investigate treatment satisfaction and overall experience of SRDs' patients receiving biologics as well as to explore patient's perspectives on the quality of services provided by rheumatology departments and to determine factors related to the level of satisfaction. We performed a synchronous correlation study. Patients with SRDs answered an anonymous questionnaire assessing their satisfaction and how treatment with biologics has affected their quality of life and functionality. Sample consisted by 244 patients (65.2% women), with mean age of 50.4 years, and the most common diagnosis was rheumatoid arthritis (37.3%). Sixty one percent of patients received intravenous therapy and 39% subcutaneously. Overall, 80.5% of the patients reported a positive/very positive effect of their treatment on their life. The average total patient satisfaction from the unit was 79.8%. The presence of mental disease was significantly associated with less positive impact of the treatment on patients' life, worse quality of life, and greater pain. In conclusion, patients with a broad spectrum of SRDs were generally satisfied and treatment with biologic regimens appeared to have a positive impact on several aspects of their life. The majority of patients were at least satisfied with all the characteristics of the unit staff and better quality of life was associated with greater satisfaction about the Unit and more positive affect of the treatment in patients' life.

Treat to target in Behcet's disease: Should we follow the paradigm of other systemic rheumatic diseases?

During the last decades the efficacy of biologic agents, mainly of anti-TNFs, in controlling the activity of serious manifestations of Behcet's Disease (BD) has been established. On the other hand, the clinical heterogeneity of BD has precluded the validation of a widely-accepted composite index for disease assessment and for target disease-state definitions, such as low disease activity and remission, and the testing of their implementation in clinical practice. Therefore, in contrast to other systemic rheumatic diseases, a treat-to-target strategy has not yet been developed in BD. There are several challenges towards this approach, including standardization of outcome measures for assessing the disease activity in each-affected organ and construction of a composite disease activity index. The challenges for the development of a treat-to-target strategy and possible solutions are discussed in this position paper, which stemmed from a round table discussion that took place in the 19th International Conference on BD.

[Assessment of pain in patients with rheumatic disease under biological therapy treatment].

BACKGROUND: To assess pain in patients with rheumatic disease under biological therapy treatment. METHODS: Observational retrospective study of patients with rheumatic disease under biological therapy treatment who visited the health care center as outpatients in February/August 2020. We collected demographic (sex and age), clinical (diagnosis, pain presence, intensity, and location), and pharmacological (biological therapy, concomitant treatment with traditional DMARDs, and analgesic treatment) variables from the electronic medical records and Farmatools Dominion®. RESULTS: We included 138 patients; mean age was 56 years and 71% were female. The most frequent diagnosis (47%) was ankylosing spondylitis. Anti-TNF-a was the most prescribed biological drug (64%); 60.1% of study patients received traditional drugs, particularly methotrexate and leflunomide (51.8 and 28.9%, respectively). Pain was reported in 81% of the cases, particularly in hands (73.2%) and knees (69.6%); mean pain intensity was 6.5 (VAS). Although 83.3% of the patients had been prescribed analgesics, pain persisted in 84.8% of the cases (VAS >4), being severe or very severe in 67.9%. Over half of the patients (52.2%) used more than one analgesic. The most frequently prescribed medications were non-steroidal anti-inflammatory drugs (NSAIDs) (60%), paracetamol (52.2%), and opioids (56.5%). NSAIDs controlled pain (14.5%) better than opioids (8.3%); there was no post-treatment improvement of pain in 29.6% of the patients. The number of prescribed drugs increased with pain intensity (rho= 0.264; p= 0.006). CONCLUSION: Almost 70% of study patients had uncontrolled severe rheumatic-related pain. This implies a challenge for esta­blishing effective treatments for this type of pain.

Systems pharmacology approach to investigate the mechanism of Artemisia argyi in treating rheumatic diseases.

Artemisia argyi (AA) has been proven to be effective in the adjuvant treatment of rheumatism (RA), but the mechanism of its action in RA is not clear. This study aims to clarify the molecular mechanism of AA as a potential therapy for RA by using network pharmacology. The TCM systems pharmacology (TCMSP) was used to screen the active components of AA, and identification of the potential target genes of active compounds and rheumatism was performed with PharmMapper and GeneCards, respectively. Construction of complex target networks and protein-protein interaction networks was based on the Cytoscape software. The biological functions and pathway analysis of targets and effective targets were analyzed using DAVID. Our study demonstrated that 105 target genes were associated with these active compounds and RA. ALB, AKT1, and MAPK1 were the first three hub genes, and the metabolic and signaling pathways related to these hub genes were remarkably abundant. Results showed that AA might play a role in RA by affecting multiple targets and multiple ways, reflecting that TCM was characterized by multicomponents and multitargets. AA has the potential to be a promising new candidate for the treatment of RA and has value for further research and development.

Targeting Multiple End Organs in Lupus and Other Systemic Rheumatic Diseases by Inhibiting Bruton's Tyrosine Kinase.

Bruton tyrosine kinase (Btk) plays a vital role in activating and differentiating B-cells and regulating signaling in myeloid cells. Indeed, the potential use of Btk inhibitors in preventing lupus has been reported. Here, we extend these observations to 4 additional models of end-organ inflammation: (a) BWF1 lupus nephritis mice, (b) anti-GBM nephritis, (c) bleomycin-induced systemic sclerosis like skin disease, and (d) bleomycin-induced lung disease. In agreement with the previous studies, BTK inhibitor (BTKB66) treatment was effective in treating lupus nephritis in terms of reducing renal damage both functionally and histologically, accompanied by significant decrease in proteinuria. Both low-dose and high-dose BTKB66 profoundly blocked renal disease in the anti-GBM nephritis model, with efficacy that was comparable to that seen with dexamethasone. This study provides the first evidence that BTK inhibition has both therapeutic and preventative effects in bleomycin-induced SSc-like disease, in terms of reducing skin thickness, fibrosis, collagen deposition, and inflammation. Likewise, significantly lower lung inflammatory cell infiltration was observed after treatment with BTKB66. Therapeutic benefit was associated with lower numbers of macrophages, proliferating macrophages and activated T-cells in the respective injured organs. The observation that these immune cells play key roles in driving end organ inflammation in multiple systemic rheumatic diseases have broad implications for the use of BTKB66 in managing patients with systemic rheumatic diseases where multiple end organs are afflicted, including lupus and systemic sclerosis.

Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study.

Background: The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods: This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. Results: In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Conclusion: Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.

Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis.

BACKGROUND: Polyunsaturated fatty acid (PUFA) supplementation has been reported to improve disease activity in inflammatory rheumatic diseases (IRDs). However, data are often conflicting and studies insufficiently large to draw conclusions. This systematic literature review and meta-analysis aimed to better estimate the effect of oral supplementation with omega (n)-3 and n-6 PUFA on IRD activity in terms of duration, dose, type, and source. METHODS: The literature was searched in PubMed, EMBASE, and Cochrane Library databases up to October 2020. Studies were reviewed in accordance with PRISMA guidelines. The effect of PUFA supplementation on disease activity was expressed as the standardized mean difference (95% CI). Metaregression and subgroup analyses involved type of IRD, Jadad score, PUFA source (animal or vegetable), and doses. RESULTS: We obtained 42 references; 30 randomized controlled studies were included comparing the effects of PUFA versus control on disease activity (710 IRD patients receiving PUFA supplementation and 710 controls, most with rheumatoid arthritis). We found a significant improvement in pain, swollen and tender joint count, Disease Activity Score in 28 joints, and Health Assessment Questionnaire score in IRD patients receiving PUFA supplementation as compared with controls, with a significant decrease in erythrocyte sedimentation rate but not C-reactive protein level. Although meta-regression revealed no difference by IRD type or source or dose of PUFA supplementation, subgroup analysis revealed more parameters significantly improved with animal- than vegetable-derived PUFAs and 3- to 6-month supplementation. Most studies examined high-dose supplementation (>2 g/day). CONCLUSION: PUFA consumption, especially omega-3 from animal source >2 g/day, may improve IRD activity and might be an adjuvant therapy in rheumatoid arthritis. TRIAL REGISTRATION: The protocol was registered at PROSPERO ( CRD42021253685 ).

Phytoconstituents and Pharmacological Activities of Indian Camphorweed (Pluchea indica): A Multi-Potential Medicinal Plant of Nutritional and Ethnomedicinal Importance.

Pluchea indica (L.) Less. (Asteraceae) commonly known as Indian camphorweed, pluchea, or marsh fleabane has gained great importance in various traditional medicines for its nutritional and medicinal benefits. It is utilized to cure several illnesses such as lumbago, kidney stones, leucorrhea, inflammation, gangrenous and atonic ulcer, hemorrhoids, dysentery, eye diseases, itchy skin, acid stomach, dysuria, abdominal pain, scabies, fever, sore muscles, dysentery, diabetes, rheumatism, etc. The plant or its leaves in the form of tea are commonly used for treating diabetes and rheumatism. The plant is a rich source of calcium, vitamin C, dietary fiber, and ß-carotene. Various biomolecules have been isolated from P. indica, including thiophenes, terpenes, quinic acids, sterols, lignans, phenolics, and flavonoids. The current review reports detailed information about the phytoconstituents and pharmacological relevance of P. indica and the link to its traditional uses. The reported studies validated the efficacy and safety of P. indica, as well as supported its traditional uses for treating various ailments and promoting health and well-being. Thus, this could encourage the development of this plant into a healthy food supplement or medicine for the prevention and treatment of various diseases. However, further studies on the drug interactions, mechanism of action, pharmacokinetics, toxicology, and metabolism, as well as clinical trials, should be carried out.

Ethnobotany, phytochemistry, pharmacology, and toxicology of the genus Sambucus L. (Viburnaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Sambucus L. (Viburnaceae) consists of about 29 recognized species distributed in all regions of the world except the extremely cold and desert areas. Some species have been used as traditional medicines to treat various disorders such as bone fractures, rheumatism, diabetes, respiratory and pulmonary disorders, skin diseases, inflammatory ailments, diarrhea, and others. However, the currently available data on traditional and pharmacological uses have not been comprehensively reviewed. STUDY AIM: The present review is designed to provide information on the ethnobotanical uses, phytochemistry, toxicity, and the known biological properties of Sambucus, to understand their connotations and provide a scientific basis and gaps for further research. MATERIALS AND METHODS: The information was obtained from different bibliographic databases, Google Scholar, Springer Link, Web of Science, PubMed, and Science Direct along with other literature sources such as dissertation before August 2021. The scientific names were validated using The Plant List and World Flora Online websites. RESULTS: Twelve Sambucus species were found to be frequently mentioned in ethnomedical uses recorded in China, Korea, Turkey, Iran, and other countries. Traditionally, they have been used as remedies to numerous health complications among others, bone fractures and rheumatism, diabetes, wounds, inflammatory diseases, diarrhea, menstrual pains, respiratory and pulmonary complaints, skin disorders, headaches, snakebites, and urinary tract infections. To date, only eleven species have been studied for their chemical compounds and a total of 425 bioactive constituents, including phenolic compounds, terpenoids, fatty acids, cyanogenic glycosides, phytosterols, lectins, organic acids, alkaloid, coumarin, anthraquinone, and others have been reported. The crude extracts and the isolated chemical constituents exhibited diverse outstanding pharmacological activities including antioxidant, antimicrobial, antidiabetic, anti-inflammatory, antidepressant, analgesic, anti-giardial, immunomodulatory, scolicidal, anti-ulcerogenic, antiradical, bone-protective, anti-glycemic, antiosteoporotic, hypolipidemic, anti-glycation, and wound-healing properties. CONCLUSION: This study summarized and scrutinized the data on traditional uses, pharmacological activities, phytochemicals, and toxicity of Sambucus species, which indicate they have interesting chemical compounds with diverse biological activities. Many traditional uses of some species from this genus have now been confirmed by pharmacological activities, such as antioxidant, antimicrobial, bone-protective, wound healing, anti-inflammatory, and analgesic properties. However, the currently available data has several gaps in understanding the traditional uses of all Sambucus species. Thus, we strongly recommend further investigations into the scientific connotations between traditional medicinal uses and pharmacological activities, mode of action of the isolated bioactive constituents, and toxicity of other Sambucus species to unravel their efficacy and therapeutic potential for safe clinical application. The current extensive study avails valuable information on therapeutic use of Sambucus species and paves way for further investigations of other useful species, as well as drug discovery.