Neurodegenerative diseases (NDDs) are one of the leading causes of death and disability in humans. From a mechanistic perspective, the complexity of pathophysiological mechanisms contributes to NDDs. Therefore, there is an urgency to provide novel multi-target agents towards the simultaneous modulation of dysregulated pathways against NDDs. Besides, their lack of effectiveness and associated side effects have contributed to the lack of conventional therapies as suitable therapeutic agents. Prevailing reports have introduced plant secondary metabolites as promising multi-target agents in combating NDDs. Polydatin is a natural phenolic compound, employing potential mechanisms in fighting NDDs. It is considered an auspicious phytochemical in modulating neuroinflammatory/apoptotic/autophagy/oxidative stress signaling mediators such as nuclear factor-κB (NF-κB), NF-E2–related factor 2 (Nrf2)/antioxidant response elements (ARE), matrix metalloproteinase (MMPs), interleukins (ILs), phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), and the extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK). Accordingly, polydatin potentially counteracts Alzheimer’s disease, cognition/memory dysfunction, Parkinson’s disease, brain/spinal cord injuries, ischemic stroke, and miscellaneous neuronal dysfunctionalities. The present study provides all of the neuroprotective mechanisms of polydatin in various NDDs. Additionally, the novel delivery systems of polydatin are provided regarding increasing its safety, solubility, bioavailability, and efficacy, as well as developing a long-lasting therapeutic concentration of polydatin in the central nervous system, possessing fewer side effects.

Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing symptoms. During SCI, inflammation, oxidative stress, apoptosis, and autophagy are behind the secondary phase of SCI and cause serious consequences. It urges the need for providing multi-targeting agents, that possess lower side effects and higher efficacy. The plant secondary metabolites are multi-targeting agents and seem to provide new roads in combating diseases. Flavonoids are phytochemicals of continual interest to scientists in combating neurodegenerative diseases (NDDs). Flavonoids are being studied for their biological and pharmacological effects, particularly as antioxidants, anti-inflammatory agents, anti-apoptotic, and autophagy regulators. Quercetin is one of the most well-known flavonols known for its preventative and therapeutic properties. It is a naturally occurring bioactive flavonoid that has recently received a lot of attention for its beneficial effects on NDDs. Several preclinical evidence demonstrated its neuroprotective effects. In this systematic review, we aimed at providing the biological activities of quercetin and related derivatives against SCI. Detailed neuroprotective mechanisms of quercetin derivatives are also highlighted in combating SCI.

: Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of Pistacia atlantica gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl3). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of P. atlantica gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl3 group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl3 exposure. Our findings suggest that P. atlantica gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.

Background: Arctium lappa L. is a well-known medicinal herb recognized for its anti-inflammatory and antioxidant properties, which have been shown to be beneficial in the treatment of various diseases. Objectives: The present study aimed to explore the protective effects of the hydroalcoholic extract of A. lappa root in complete Freund’s adjuvant (CFA)-induced arthritis in rats. Methods: Arthritis was induced in Sprague-Dawley rats through a single subcutaneous CFA injection into the right hind paws. After induction, the animals were orally administered A. lappa at doses of 200 and 400 mg/kg, or prednisolone (as a reference drug), for a duration of 30 days. Blood and ankle joint samples were collected for analysis. The anti-arthritic effects were assessed through nociceptive behavioral tests, paw edema, body weight measurements, serum concentrations of tumor necrosis factor-α (TNF-α), nitric oxide (NO), glutathione (GSH), superoxide dismutase (SOD) activity, and histopathological evaluations. Results: The A. lappa root extract significantly improved body weight and reduced thermal hyperalgesia, as well as decreased paw edema in a dose-dependent manner (P < 0.001). Furthermore, A. lappa reduced inflammatory cytokines and increased antioxidant defenses in the serum of all treated rats (P < 0.05 to P < 0.001). Histologically, A. lappa notably restored the ankle joint architecture compared to untreated arthritic rats (P < 0.05 to P < 0.001). Conclusions: The results suggest that A. lappa has significant anti-arthritic potential by reducing inflammatory cytokines and enhancing serum antioxidant levels, which supports its traditional use in the management of joint diseases.

Background: Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal conditions such as Crohn's disease and ulcerative colitis (UC). Despite their differing pathophysiologies, these conditions are influenced by common factors, including genetics, environmental influences, and gut microbiota. Recent studies suggest that oxidative stress significantly contributes to intestinal inflammation. Additionally, medicinal plants are recognized for their efficacy in treating various illnesses, forming the basis of many modern medications. Objectives: This study investigated the potential of rutin, a natural compound, by synthesizing it into nanoparticles. These rutin nanoparticles were designed to enhance drug solubility and intestinal absorption, thereby improving therapeutic efficacy and shelf life. Methods: Thirty adult rats were divided into six groups for this experiment. Excluding the control group, all were treated with 2 mL of 4% acetic acid (AA) followed by sulfasalazine. Subsequently, three different dosages of rutin nanoparticles (100, 150, and 200 mg/kg) were administered. The evaluation included tests for glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-α), as well as macroscopic and microscopic analyses. Results: Intracolonic administration of AA resulted in severe acute inflammation in the colonic tissue, which was improved by rutin nanoparticles in both microscopic and macroscopic aspects. Additionally, rutin nanoparticles modified TNF-α and oxidative stress-related markers, including GSH, NO, and SOD levels. Conclusions: Our results indicate that rutin nanoparticles exhibit significant therapeutic effects in treating UC. These findings suggest the potential of natural products and their nanoparticle formulations in treating inflammatory diseases.