Piperine, the principal bioactive alkaloid of Piper nigrum and Piper longum, has emerged as a promising phytotherapeutic candidate for the management of osteoarthritis (OA), a prevalent degenerative joint disease and a leading cause of chronic pain, disability and reduced quality of life worldwide. Its therapeutic potential is attributed to a wide range of pharmacological activities, including anti-inflammatory, antioxidant, analgesic, immunomodulatory and chondroprotective effects. The increasing burden of OA, driven by population aging, obesity, and metabolic disorders, highlights the urgent need for safer and more effective therapeutic strategies, as current treatments mainly provide symptomatic relief and no disease-modifying osteoarthritis drugs have been approved for clinical use. This review comprehensively discusses the pathophysiology of OA, the molecular mechanisms underlying the therapeutic effects of piperine, and emerging translational strategies aimed at improving its clinical translation for OA management and cartilage regeneration. This narrative review examined experimental evidence on the pharmacological activities of piperine and evaluated recent advances in piperine-based delivery systems, including nanocarriers, polymeric matrices, biomimetic scaffolds, tissue-engineering constructs, and controlled-release formulations, with emphasis on their potential applications in OA management. Piperine may modulate OA-associated inflammatory and catabolic pathways, although its therapeutic efficacy and disease-modifying potential remain investigational. However, limited aqueous solubility, reduced systemic bioavailability, rapid metabolic clearance, and short systemic retention limit its clinical application. Advanced delivery systems may overcome these limitations by improving stability, enabling targeted delivery, enabling sustained release, and enhancing local therapeutic efficacy within the joint microenvironment. Piperine is a potential phytotherapeutic candidate for OA owing to its multifaceted pharmacological activities. Novel delivery strategies could address its pharmacokinetic limitations and accelerate its translation into clinically effective therapies for OA.
Current therapies for asthma are limited by significant adverse effects, and many patients with severe asthma are still unable to achieve adequate symptom control, highlighting the need for novel therapeutic strategies. Fucosylated chondroitin sulfate (FucCS), a glycosaminoglycan isolated from the sea cucumber Holothuria grisea, demonstrates anti-inflammatory properties. This study investigated the therapeutic potential of FucCS in a murine model of ovalbumin (OVA)-induced allergic airway inflammation. C57BL/6 mice were sensitized and challenged with OVA and then treated intraperitoneally with FucCS (2 mg/kg), dexamethasone (DEXA, 2 mg/kg, positive control), or saline (SAL, vehicle control). Additional control mice received saline (CTRL/SAL) instead of OVA during both sensitization and challenge. Pulmonary function, the extent of peribronchial inflammation, total and differential cell counts in bronchoalveolar lavage fluid (BALF) and lung tissue, as well as levels of key inflammatory mediators were assessed. Compared to the OVA/SAL group, treatment with FucCS significantly reduced basal airway resistance, peribronchial inflammation, and polymorphonuclear cell infiltration in lung parenchyma. Furthermore, FucCS therapy attenuated BALF total cellularity and interleukin (IL)-4 levels and reduced IL-5 levels in lung homogenates, with effects comparable to dexamethasone. Neither treatment altered BALF eosinophil percentage. These findings demonstrate a limited, but significant anti-inflammatory effects of FucCS in experimental allergic inflammation and support its further development as a therapeutic candidate.
Inflammation is one of the main underlying causes of many diseases. Despite the fact that existing anti-inflammatory treatments like NSAIDs and corticosteroids can effectively treat inflammation, the use of these medicines clinically poses several problems due to serious side effects and poor specificity. Bee venom (BV) has emerged as a promising natural treatment for its anti-inflammatory and immunomodulatory properties due to the presence of biologically active compounds such as melittin and phospholipase A2 (PLA2). BV modulates multiple inflammatory signaling pathways by inhibiting NF-κB activation, suppressing MAPK signaling, downregulating inducible nitric oxide synthase (iNOS) and cyclooxygenase−2 (COX-2), promoting regulatory T-cell (Treg) polarization, and activating the Nrf2/HO-1 antioxidant pathways. Furthermore, BV enhances wound healing by macrophage polarization, regulation of NF-κB, MAPK, Nrf2/HO-1, and ROS signaling, inhibition of PI3K/Akt signaling, suppression of TGF-β-induced pro-fibrotic gene expression, and cytokine modulation to promote tissue regeneration. The therapeutic efficacy of BV constituents has been increased due to the recent advancement in the field of nanotechnology by improving the stability, bioavailability, targeted delivery, and toxicity. In the context of parallel network pharmacology, PPI network analysis, GO enrichment, KEGG pathway analysis, molecular docking studies, and molecular dynamics simulation have shed light on the interactions of BV constituents with various inflammatory peptides. By integrating molecular pharmacology, nanomedicine, and computational approaches, this review provides a comprehensive overview of the therapeutic potential of BV bioactive compounds and highlights future opportunities for their development as multi-target anti-inflammatory candidates. However, further experimental and clinical studies are required to establish their efficacy, safety, pharmacokinetic profiles, and therapeutic applicability.
Fibromyalgia is a syndrome characterised by widespread chronic pain, often accompanied by comorbidities such as fatigue, anxiety, and depression. Pharmacological treatments offer only partial relief of symptoms and can cause significant adverse effects. Therefore, finding new treatments is crucial. Psychotria nemorosa, a species rich in indole alkaloids, has garnered interest due to its acute antinociceptive properties observed in vivo and its effects on monoamine oxidase A and B in in vitro assays. Additionally, alkaloids are recognised for their antinociceptive effects, as well as their anxiolytic and antidepressant properties. Therefore, we examined the effects of the alkaloid fraction of P. nemorosa in a model that simulates fibromyalgia symptoms in male Swiss. Initially, the antinociceptive effects of the fraction (3, 10, and 30 mg/kg, administered orally) were tested in capsaicin- and formalin-induced nociception, and potential adverse effects on locomotion and body temperature were evaluated. Next, the 30 mg/kg dose was tested in the reserpine-induced fibromyalgia model for mechanical, cold, and heat sensitivity, muscle strength, and behaviours resembling depression and anxiety. The P. nemorosa alkaloid fraction (30 mg/kg) decreased capsaicin- and formalin-induced nociception without affecting locomotion or body temperature. It also alleviated mechanical and cold allodynia, thermal hyperalgesia, muscle fatigue, and anxiety-like behaviour caused by reserpine, although it did not show an antidepressant-like effect. These results suggest that the P. nemorosa alkaloid fraction has therapeutic potential for treating fibromyalgia pain and related conditions such as fatigue and anxiety. They also emphasise the need for further research into its mechanisms and its long-term safety.
Parkinson’s disease is a progressive neurodegenerative disorder characterized by degeneration of dopaminergic neurons, resulting in tremor, rigidity, bradykinesia and poor motor coordination. The present study was aimed to evaluate anti-Parkinsonian activity and neuroprotective potential of cardamonin in reserpine and haloperidol induced experimental models of Parkinsonism in mice. Cardamonin is a naturally occurring chalcone that has been reported to possess antioxidant and anti-inflammatory activities and may modulate biological processes associated with oxidative stress and neuroinflammation. Motor and cognitive functions were assessed using behavioral tests including open-field, pole-climbing, catalepsy and novel object recognition tests. Biochemical estimations of lipid peroxidation and endogenous antioxidants status were performed. Further, the tissue levels of dopamine were estimated. Brain tissues were subjected to routine histopathological investigation. Results showed that cardamonin significantly improved motor activity, decreased oxidative stress, enhanced the status of endogenous antioxidants and increased tissue levels of dopamine. Histopathological examination showed attenuation of general histological changes in treated animals. To summarize, the results support the anti-Parkinsonian activity and neuroprotective potential of cardamonin under the experimental conditions. However, direct preservation of dopaminergic neurons was not demonstrated because dopaminergic neuron-specific markers were not evaluated.
