Objective: To investigate the mechanisms by which unripe papaya extract (UCP) protects skin keratinocytes from UVB-induced inflammation and apoptosis. Methods: High-performance liquid chromatography was used to identify the phytochemical composition of UCP. The free radical scavenging capacity of UCP was assessed against O 2 .- , and H 2 O 2 . HaCaT cells were pre-treated with varying concentrations of UCP and exposed to 40 mJ/cm 2 UVB radiation. Cell viability, reactive oxygen species (ROS) levels, apoptotic markers, and inflammatory mediators were evaluated using standard biochemical assays and molecular techniques. Results: UCP treatment significantly improved cell viability and reduced intracellular ROS and the release of O 2 .- and H 2 O 2 . UCP also inhibited apoptosis, as evidenced by reduced cytochrome c release and suppression of Akt phosphorylation. Additionally, UCP exhibited anti-inflammatory effects by downregulating COX-2 expression, suppressing PGE 2 release, and inhibiting c-Jun and NF-κB signaling pathways. Conclusions: UCP effectively protects skin keratinocytes from UVB-induced oxidative stress, inflammation, and apoptosis. These findings support its potential as a natural therapeutic agent for preventing UV-related skin damage. However, in vivo studies are warranted to confirm its efficacy.

Objective: To investigate whether nacre extract improves insulin sensitivity, brain glucose metabolism, and cognitive function in diabetic mice. Methods: Diabetic KK-Ay mice ( n =5/group) were fed a standard diet or diets supplemented with nacre extract (125 or 250 mg/kg) for 13 weeks. Metabolic status was assessed by measuring fasting glucose and insulin levels, HOMA-IR, glucose tolerance, and insulin tolerance. The expression of IRS-1, IRS-2, and GLUT4 in the brain was analyzed by qPCR, Western blotting, and immunohistochemistry. Cognitive and anxiety-like behaviors were evaluated using the Y-maze, novel object recognition, Barnes maze, and open field tests. Results: Nacre extract significantly reduced fasting glucose and insulin levels, improved HOMA-IR, and enhanced glucose and insulin tolerance ( P <0.05) in diabetic mice. It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF. Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors. Conclusions: Nacre extract enhances insulin sensitivity, improves brain glucose metabolism, and alleviates cognitive and emotional dysfunction in diabetic mice. Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.

Objective: To assess the protective effects of Panax ginseng (PG) against copper sulfate (CuSO 4 )-induced kidney toxicity in rats. Methods: The rats were randomly allocated into four groups: control, CuSO 4 , PG, and PG+CuSO 4 . The experiment continued for 14 days, during which CuSO 4 was provided at a dosage of 100 mg/kg body weight per day and PG at 300 mg/kg body weight by oral gavage per day. Upon completion of the experiment, kidney sections were used for histological and histomorphometric analyses. The histochemical method was applied to ascertain the density of the glomerular mesangial matrix. The expressions of vascular endothelial growth factor (VEGF) and caspase-3 were examined using immunohistochemistry. The levels of malondialdehyde and glutathione, along with the activity of superoxide dismutase and catalase in the kidney, were measured. Results: PG treatment exhibited a marked protective effect against CuSO4-induced renal damage, as evidenced by improved histopathological lesions, significantly reduced glomerular mesangial matrix density, VEGF in distal tubules, caspase-3 expression, and malondialdehyde levels in renal tissue, as well as enhanced superoxide dismutase and catalase activities. Conclusions: PG treatment ameliorates CuSO 4 -induced kidney injury in rats. Further studies are warranted to verify its efficacy and elucidate the underlying mechanism of its nephroprotective 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 isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210 °C (GCSW210) and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese zebrafish larvae. Methods: GCSW210 was fractionated through solvent partitioning, ion-exchange chromatography, and silica gel medium-pressure liquid chromatography, followed by preparative high performance liquid chromatography. At each step, bioactivities were assessed in 3T3-L1 adipocytes by Oil Red O staining and 2-NBDG uptake assays. The most active fractions were further purified, and isolated compounds were tested in HFD-induced obese zebrafish larvae. Results: Liquid chromatography-hyphenated analysis with reference standards identified two major compounds in GCSW210: 5-hydroxymethylfurfural and bis(5-formylfurfuryl) ether. Both compounds significantly inhibited lipid accumulation in 3T3-L1 adipocytes and modulated gene expression associated with adipogenesis, glucose metabolism, and inflammation in zebrafish. They also enhanced glucose uptake, reduced circulating glucose levels, and improved insulin sensitivity. Notably, the effects were comparable to those of the crude GCSW210 extract. In silico docking studies confirmed stable interactions of both compounds with key metabolic and inflammatory targets, with bis(5-formylfurfuryl) ether showing stronger binding affinities. Conclusions: These findings suggest that 5-hydroxymethylfurfural and bis(5-formylfurfuryl) ether are key contributors to the therapeutic activity of Gracilaria chorda , highlighting its potential as a functional food ingredient for the prevention or management of metabolic disorders.

Crocin is a plant ingredient mainly found in the extract of Crocus sativus (Saffron). This carotenoid compound has antioxidant, anti-inflammatory, antitumor, and antihypertensive properties. This review summarizes the therapeutic effects of crocin. Data were retrieved from 2015 until the end of April 2025 using databases including the Web of Science, PubMed, Scopus, and Google Scholar. According to the findings of previous studies, the therapeutic effects of crocin on various organs can be attributed to its ability to scavenge free radicals, enhance antioxidant activities, reduce inflammatory reactions, and modulate the PI3K/AKT, NF-κB, and PPARγ/LXRs signaling pathways.

Objective: To evaluate the hepatoprotective effects of the ethanol fraction of Verbascum thapsus L. (EFVT) against CCl 4 -induced liver injury and elucidate its underlying mechanisms. Methods: The assessment of antioxidant properties and cell viability was conducted using the 2,2-diphenyl-1-picrylhydrazyl assay and HepG2 cells, respectively. The in vivo hepatoprotective efficacy of EFVT was evaluated in a rat model of carbon tetrachloride (CCl 4 )-induced liver injury by determining biochemical parameters, and oxidative stress- and inflammation-related markers. Gas chromatography-mass spectrometry was also employed for the qualitative analysis of its phytochemical composition. Results: GC-MS analysis of EFVT revealed the presence of several bioactive compounds such as 3 methyl mannoside and 9,12-octadecadienoic acid. Oral administration of EFVT significantly mitigated CCl 4 -induced liver injury, as evidenced by reduced levels of total bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and malondialdehyde, boosted activities of catalase and superoxide dismutase, as well as enhanced glutathione levels. Histopathological examinations indicated EFVT restored abnormal liver architecture and reduced inflammation. Additionally, EFVT substantially downregulated the mRNA levels of IL-6, IL-1β, TNF-α , and NF-κB , and upregulated IL-10 expression. Conclusions: These findings underscore the therapeutic potential of EFVT in ameliorating liver damage associated with oxidative stress, providing scientific validation for its traditional utilization in ethnomedicine.

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 investigate the osteogenic effects of polyphenol-rich extracts from Wisteria floribunda (Willd.) DC. (W. floribunda) flowers and elucidate the underlying mechanisms. Methods: Polyphenolic compounds of W. floribunda extracts were analyzed, including flavonoids and glucoside derivatives. Osteogenic activity was assessed in MC3T3-E1 preosteoblast cells by measurement of alkaline phosphatase (ALP) activity, alizarin red S staining, and the expression of osteogenic markers (RUNX2, SP7, and ALPL). In vivo effects were evaluated in zebrafish larvae by assessing skeletal development and expression of osteogenic genes (runx2a, sp7, and alpl). The role of mammalian target of rapamycin (mTOR) pathway was examined using rapamycin. Results: W. floribunda extracts significantly enhanced ALP activity, bone mineralization, and the expression of RUNX2, SP7, and ALPL in MC3T3-E1 cells. In zebrafish larvae, W. floribunda extracts improved vertebral mineralization and upregulated osteogenic genes. Mechanistically, the plant extract activated the mTOR pathway, and rapamycin treatment attenuated the extracts-induced ALP activity, mineralization, and vertebral formation in zebrafish, confirming mTOR involvement. Conclusions: W. floribunda extracts promote osteoblast differentiation and bone formation via mTOR pathway activation. These findings provide novel insights into the potential of W. floribunda extracts and support its further investigation as a natural therapeutic candidate for bone degenerative disorders such as osteoporosis.

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.