Plantago major L., commonly known as plantain, waybread, or dooryard plantain, is a versatile medicinal plant with multiple therapeutic applications. Traditionally, various parts of the plant have been formulated into syrups, drops, ointments, vaginal suppositories, gargles, and roasted preparations to treat diverse ailments, such as liver disorders, earaches, epilepsy, asthma, stomachaches, diarrhea, constipation, polymenorrhea, and uterine disorders. The plant contains clinically valuable bioactive compounds, including polysaccharides, flavonoids, lipids, iridoid glycosides, caffeic acid derivatives, terpenoids, alkaloids, and organic acids. These bioactive constituents are the primary contributors to the plant’s broad spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, antidiarrheal, hepatoprotective, antiviral, antiphage, antinociceptive, antiulcerogenic, antigenotoxic, and immunomodulatory effects of the plant. This review comprehensively summarizes the phytochemical composition, traditional medicinal applications, and biological properties of this multifunctional medicinal plant.

Objective: To investigate the anti-atherosclerosis effect of chikusetsusaponin IV (CSIV) against high-fat diet-induced atherosclerosis in rats. Methods: A high-fat diet was used for the induction of atherosclerosis in rats, and the rats received oral CSV or atorvastatin. The body weight, organ weights, food intake, calorie intake, lipid parameters, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)/mevalonate ratio, collagen, free fatty acid, cardiac parameters, apolipoprotein (A and B), antioxidant parameters, inflammatory cytokines, and inflammatory parameters were assessed. The mRNA expressions of interleukin-1β ( IL- β), tumor necrosis factor-α (TNF-α), IL -6, IL -17, PI3K , AKT , and mTOR were estimated. Results: CSV significantly modulated food intake, body weight, organ weight (liver, kidney, and heart), and calories ( P <0.05). Total cholesterol, triglycerides, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, cardiovascular risk index-1, and cardiovascular risk index-2 were decreased, while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSV group ( P <0.05). Besides, CSV significantly restored the level of HMG-CoA/mevalonate ratio, collagen, free fatty acid, cardiac parameters (creatinine kinase-MB, lactate dehydrogenase, cTnT, cTnI), apolipoprotein (apolipoprotein A and apolipoprotein B), antioxidant parameters (MDA, CAT, GPx, GSH, SOD), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), inflammatory parameters (COX-2, TGF-β, NF-κB), intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1. CSV also decreased the mRNA expression of IL-1β , TNF -α, IL -6, IL -17, PI3K , AKT , and mTOR . Conclusions: This study showed the anti-atherosclerosis effect of CSV against high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.

Ruscogenin, a steroidal sapogenin, is primarily derived from the genus Ruscus. It demonstrates a wide range of pharmacological actions that hold substantial promise for therapeutic use. By conducting a comprehensive examination of electronic databases including PubMed, ScienceDirect, and SciFinder, we identified studies on ruscogenin to date. This review aims at emphasizing the findings related to the bioactivities of ruscogenin, particularly its protective activities in neurological and inflammatory disorders, hemorrhoids, and cancer. Ruscogenin has been demonstrated to possess anti-ulcer, anti-osteoporotic, and skin-lightening properties as a therapeutic agent. It has also been proven effective in managing metabolic disorders by reducing inflammation and improving lipid metabolism, particularly in conditions such as non-alcoholic steatohepatitis and diabetic nephropathy. Reports indicate that it can prevent acute lung injury by protecting pulmonary endothelial cells from apoptosis and modulating inflammatory cytokines. Additionally, ruscogenin promotes neurological recovery by mitigating oxidative stress. It also shows anti-cancer properties, leading to apoptosis and hindering metastasis, particularly in pancreatic and hepatocellular carcinoma. This review summarizes the potential medical applications of ruscogenin and underscores the need for further research on its mechanisms of action.

Objective: To investigate the effect of cerebrolysin (CBL) on motor impairment, neuroinflammation, oxidative stress, and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) in zebrafish. Methods: In the current study, zebrafish were treated with CBL at doses of 1.25, 2.5, and 5 mL/kg body weight for 7 consecutive days. MPTP (20 mg/kg body weight) was administered on alternative days-lst, 3rd, 5th, and 7th. On day 7, zebrafish were sacrificed, and their brains were isolated for biochemical, neurochemical, histopathological, IHC, and neurotransmitter analysis. Results: The treatment with CBL significantly increased total distance traveled and the number of entries in the top zone, which was impaired by MPTP. CBL treatment significantly restored the level of glutathione, superoxide dismutase, and catalase while reducing malondialdehyde level. It also reduced the level of pro-inflammatory mediators interleukin-1β, interleukin-6, and tumor necrosis factor-α in the MPTP-induced PD in the zebrafish model. In histopathological evaluation, pyknotic cells and signs of inflammation were significantly reduced in CBL-treated groups. A significant dose-dependent reduction in glutamate, along with elevations in dopamine, gamma-aminobutyric acid, serotonin, and noradrenaline, was observed in zebrafish treated with CBL. An immunohistochemistry analysis demonstrated that Akt was phosphorylated promptly by CBL, which was downregulated in MPTP-induced PD in zebrafish. Conclusions: These findings suggest that CBL exerts a neuroprotective effect through activation of Akt and may hold therapeutic potential for the treatment of this devastating neurological condition.

Objective: To investigate the potential of hydro-alcoholic extract of Gentiana lutea roots (GLE) in scopolamine-induced amnesia model in mice. Methods: The active chemical constituents were determined by GC-MS analysis. In vitro antioxidant activity was performed by the DPPH free radical scavenging method. Ex vivo anti-acetylcholinesterase assay was conducted to investigate the effect on the cholinergic system. A scopolamine-induced memory impairment model was used. The levels of beta-amyloid (Aβ) and tau protein were measured. The behavioral studies were performed through Morris water maze and passive avoidance learning tests, followed by estimation of biochemical markers (GSH and MDA), immunohistochemistry, and histopathological studies on isolated brain tissues. Results: GLE exhibited DPPH free radical scavenging activity with an IC 50 value of (76.68±2.28) μg/mL. GLE also manifested inhibitory effect on acetylcholinesterase [IC 50 (36.58±0.73) μg/mL] to upregulate the cholinergic system. GLE at 200 mg/kg and 400 mg/kg significantly restored the memory impairment induced by scopolamine. GLE at 200 mg/kg and 400 mg/kg significantly reduced brain oxidative stress ( P <0.001). Immunohistochemistry investigation showed a significant reduction in Aβ deposition and p-tau protein expression in the GLE treatment groups ( P <0.001). Administration of GLE effectively reduced scopolamine-induced neuronal damage in a dose-dependent manner. Conclusions: The study demonstrates that GLE ameliorates scopolamine-induced memory impairment by alleviating Aβ/p-tau protein accumulation and upregulation in the cholinergic system to improve cognitive dysfunction and behavioral problems.

Objective: To examine the effect of shikonin against streptozotocin (STZ)-induced diabetic retinopathy in rats and elucidate the underlying mechanisms. Methods: Intraperitoneal administration of STZ (65 mg/kg) was used for the induction of diabetic retinopathy in rats. Rats received oral administration of shikonin (10, 20, and 30 mg/kg). The blood glucose level, insulin, body weight, and organ weight were estimated. Advanced glycation end products (AGEs) levels in serum and lens as well as protein carbonyl content of the lens were determined. The parameters related to oxidative stress and inflammation, and the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were also measured. In addition, quantitative RT-PCR was performed to determine the mRNA expressions. Results: Shikonin treatment decreased glucose level and boosted insulin level, along with an increase in body weight and improved organ weight. It also lowered O2 •-, ONOO-, serum and lens AGEs, and protein carbonyl content. Furthermore, shikonin treatment significantly alleviated oxidative stress and inflammation, as evidenced by reduced malonaldehyde, nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, cyclooxygenase-2, prostaglandin E2, protein carbonyl content, and nuclear factor kappa-B, and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase. Markedly decreased levels of ICAM-1 and VCAM-1, as well as heightened levels of Nrf2 and HO-1, were noticed after treatment with shikonin. Furthermore, the mRNA expressions of TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, RAGE, collagen IV, and fibronectin were significantly downregulated. Conclusions: Shikonin exhibits protective effects against STZ-induced diabetic retinopathy in rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways.

Objective: To investigate the protective effects of naringin on doxorubicin (DOX)-induced liver injury. Methods: A total of 50 male rats were allocated into five groups: the control group, the DOX group, the DOX groups treated with 50 mg/kg and 100 mg/kg of naringin by gastric lavage for 10 days, as well as the group treated with 100 mg/kg of naringin alone. Liver and serum samples were collected for biochemical, histopathological, and molecular analyses, including liver enzyme activity, oxidative stress markers, inflammation, apoptosis-related proteins, and DNA damage indicators. Results: Naringin attenuated DOX-induced elevation in liver enzyme activity and inflammation markers while enhancing antioxidant activities. Naringin also activated the Nrf2-HO-1 signaling pathway, with the most pronounced effect in the high-dose naringin group. In addition, naringin modulated apoptotic signaling by downregulating the expression of PI3K-AKT and BAX, and upregulating Bcl-2, as well as reduced the level of 8-OHdG. Histopathological evaluation showed that DOX-induced structural liver alterations, such as cellular degeneration and necrosis, were notably attenuated by naringin treatment. Conclusions: Naringin treatment exerts protective effects against DOX-induced liver injury through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

Moringa oleifera (M. oleifera) Lam. (family Moringaceae) possesses anti-inflammatory, anticancer, anti-diabetic, neuroprotective, and cardioprotective properties. The present review aimed to explore the protective effects of M. oleifera Lam. against metabolic disorders and to serve as a guide for future research on this medicinal plant. Research data on the anti-diabetic and anti-obesity properties of M. oleifera Lam. were collected from Science Direct, PubMed, Springer, Google Scholar, Web of Science, etc. M. oleifera has a protective effect against metabolic disorders through the modulation of various signaling pathways involved in glucose and lipid metabolism. Specifically, M. oleifera enhances insulin sensitivity by activating insulin receptor phosphorylation and the PI3K/Akt pathway, which promotes glucose uptake by facilitating GLUT-4 translocation to the cell membrane. In addition, it improves energy homeostasis and lipid metabolism by modulating the AMPK pathway. Inhibition of inflammatory biomarkers (nuclear factor kappa B, tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1) and lipid peroxidation markers (malondialdehyde, F2-isoprostanes), along with enhanced activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase), contributes to its anti-diabetic and anti-obesity effects. This review suggests that M. oleifera Lam. modulates key signaling pathways involved in glucose and lipid metabolism and holds promise as a potential therapeutic agent for managing metabolic diseases.

Type 2 diabetes mellitus (T2DM) emerges as a global health crisis and is characterized by hyperglycemia, insulin resistance, and oxidative stress. Conventional treatments for T2DM often have limitations, thus prompting interest in natural alternatives like fennel. This review explores fennel's potential anti-diabetic properties, focusing on its antioxidant and anti-inflammatory effects. Fennel contains various bioactive compounds, including flavonoids, phenolic acids, and volatile oils, known for their antioxidant properties. These compounds can neutralize free radicals and reduce oxidative stress, which plays a crucial role in T2DM. Additionally, fennel's anti-inflammatory effects may help mitigate the chronic inflammation associated with T2DM. Preclinical studies have demonstrated fennel's ability to lower blood glucose levels, improve insulin sensitivity, and reduce oxidative stress in diabetic animals. These findings suggest that fennel may be a promising natural agent for managing T2DM. However, further research is needed to fully understand its mechanisms of action and to evaluate its efficacy and safety in human clinical trials.

Objective: To investigate the protective effects of Lepidium draba L. (L. draba) on cyclophosphamide (CP)-induced hepatotoxicity and nephrotoxicity in rats. Methods: A total of 36 rats were divided into six groups as follows: the sham control group, the CP group (CP 100 mg/kg i.p. on days 1, 7, 14, 21, 28, and 35), the CP groups treated with L. draba extract (100, 200 and 400 mg/kg of L. draba extract for 28 d), and the L. draba extract alone group (400 mg/kg of L. draba extract for 28 d). Serum parameters of renal and hepatic function, as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured. Moreover, Bax, Bcl-2, and caspase-3 gene expression and histopathological changes were assessed. Results: L. draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide, TBARS, IL-6, TNF-α, and IL-Ιβ levels, as well as increasing superoxide dismutase, catalase and glutathione peroxidase activities, and FRAP, MIF, and TGF-β levels. In addition, the extract downregulated the expression of pro-apoptotic genes (Bax and caspase-3) and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes. Conclusions: L. draba extract can protect hepatic and renal structure and function against CP-induced toxicities, and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.