Pinostrobin: A Multifunctional Flavonoid with Potential Therapeutic Applications

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Pinostrobin (C16H14O4) is a flavonoid compound derived from traditional Chinese herbs such as Carya cathayensis leaves, Boesenbergia rotunda, and propolis. With a molecular weight of 270.28 daltons, pinostrobin exhibits a wide range of pharmacological effects, making it a potential candidate for the treatment of various diseases.

This article provides a comprehensive overview of the pharmacological properties of pinostrobin, emphasizing its anti-infective, lipid-lowering, anticancer, and anti-inflammatory effects.

Figure 1. Pharmacological effects of pinostrobin. Pinostrobin is widely present in many traditional Chinese herbs, including Carya cathayensis leaves, Boesenbergia rotunda and propolis. Pinostrobin exhibits many pharmacological activities, such as antitumor, anti-inflammatory, neuroprotective, and lipid-lowering effects, and it can inhibit infection, reduce uric acid, and protect multiple organs.

Chemical Properties and Sources:

Pinostrobin’s chemical structure, with chiral differences impacting its pharmacodynamics, influences its multifunctional therapeutic potential. The compound is primarily metabolized by glucuronidation through nonrenal routes, accumulating higher concentrations in the liver and gastrointestinal tract. Found in traditional Chinese herbs like Carya cathayensis leaves, Boesenbergia rotunda, and propolis, pinostrobin has gained attention for its safety and efficacy.

Anti-Infective Properties:

  • Antiviral Effects:
    • Pinostrobin inhibits herpes simplex virus type 1 (HSV-1) by binding to glycoprotein gD, preventing viral adsorption and replication.
    • Against SARS-CoV-2 and HCoV-OC43, pinostrobin binds to the main protease, inhibiting viral activity.
  • Antibacterial and Antifungal Effects:
    • Pinostrobin exhibits antibacterial effects against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and others.
    • It inhibits biofilm formation and reduces minimum effective concentrations when combined with ciprofloxacin.
    • Antifungal activity involves inhibition of yeast growth and reduction of Candida albicans invasion.
  • Antiparasitic Effect:
    • Pinostrobin demonstrates cysticidal activity and inhibits parasites like Giardia, Leishmania, and Trypanosoma americanum.

Lipid Metabolism:

  • Effects on Lipid Metabolism:
    • Pinostrobin alters lipid metabolomics, reducing triglyceride levels and inhibiting adipogenic differentiation.
    • It regulates key transcription factors and markers associated with lipid metabolism, influencing the MAPK and AKT signaling pathways.
  • LDL Cholesterol Reduction:
    • Pinostrobin competitively binds to the promoter of PCSK9, reducing LDL cholesterol levels and mitigating atherosclerosis-related risks.

Uric Acid Reduction:

  • Reduction of Uric Acid:
    • Pinostrobin decreases uric acid levels by inhibiting xanthine oxidase, a crucial enzyme in uric acid production.

Anticancer Effects:

  • Broad Antitumor Activity:
    • Pinostrobin inhibits various cancer cells through interactions with key molecules involved in cancer progression.
    • It induces apoptosis, inhibits cancer stem cell proliferation, and reverses multidrug resistance in cancer cells.
  • Leukemia Treatment:
    • Pinostrobin exhibits potential in leukemia treatment by modulating key pathways, inducing apoptosis, and promoting differentiation of leukemia cells.

Anti-Inflammatory Effects:

  • Protection Against Gastric Mucosal Injury:
    • Pinostrobin offers protection against alcohol-induced gastric mucosal injury, peptic ulcers, and inflammatory responses.
  • Inhibition of Inflammatory Responses:
    • Pinostrobin directly binds to MD2 and TLR4, inhibiting LPS/NF-κB-induced expression of proinflammatory factors in macrophages.
    • Demonstrates anti-inflammatory effects by reducing IL-6, IL-1β, TNF-α levels in various cell types and animal models.


Multiple Organ Protection:

Due to its robust antioxidant and anti-inflammatory effects, pinostrobin emerges as a versatile compound for protecting various organs against injury caused by different factors.

  • Skin:
    • Pinostrobin absorbs ultraviolet light in the harmful wavelength range of UVB and UVA, suggesting its potential role in skin protection.
    • It has shown inhibitory effects on the contraction of intestinal smooth muscle, indicating a potential use in treating diarrhea pending further in vivo investigation.
  • Detoxification Properties:
    • Pinostrobin demonstrates detoxification properties by inhibiting bothrops asper venom activity in vitro and in vivo.
    • It also alleviates phospholipase A2-induced myotoxicity, edema, and coagulation in a dose-dependent manner.

Organ-Specific Protective Effects:

  • Liver:
    • Pinostrobin protects against thioacetamide-induced liver injury in rats by increasing antioxidant enzyme activities and reducing oxidative stress and lipid peroxidation.
    • It modulates inflammatory cytokines, reducing TNF-α and IL-6 levels and increasing IL-10, leading to decreased cellular inflammation.
  • Kidney:
    • Treatment with pinostrobin reduces cyst formation in polycystic kidney mice by inhibiting CFTR-mediated transepithelial chloride secretion.
    • Mechanistically, pinostrobin inhibits fluid secretion, cell proliferation, and ERK phosphorylation levels, contributing to the reduction of cyst expansion.
  • Bone:
    • Pinostrobin, found in Blainvillea acmella extract, promotes osteoblast proliferation, differentiation, and mineralization, essential for bone formation.
    • It reverses the inhibitory effects of dexamethasone on osteoblast differentiation and increases the expression of osteocalcin in a dose-dependent manner.
  • Reproductive System: Testis and Ovary:
    • Pinostrobin mitigates the adverse effects of polystyrene microplastics on the testis, reducing oxidative stress, inflammation, and apoptosis.
    • In the ovaries, pinostrobin recovers ovarian histoarchitecture, decreases oxidative stress, and modulates hormone levels, providing protection against methotrexate-induced ovarian toxicity.
  • Stomach:
    • Pinostrobin protects against Helicobacter pylori activity and ethanol-induced gastric injury, reducing ulcer area, mucosal contents, submucosal edema, and leukocyte infiltration.

Neuroprotective Effects:

  • General Neuroprotective Effect:
    • Pinostrobin, derived from Cajanus cajan leaves, exhibits neuro-modulatory and protective effects.
    • It binds to serotonin, adrenoceptor, and GABAA receptors, showing promise in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.
  • Alzheimer’s Disease:
    • Pinostrobin inhibits BACE1 activity, a key enzyme in Aβ production, potentially reducing Aβ deposition in Alzheimer’s disease.
    • It also protects against Aβ25–35-mediated apoptosis, attributed to its antioxidant effects and inhibition of intracellular Ca2+ influx.
  • Parkinson’s Disease:
    • In a zebrafish model of Parkinson’s disease, pinostrobin attenuates neurotoxin-induced neuronal loss and behavioral disturbances.
    • Pinostrobin activates the PI3K/AKT and ERK pathway, promoting Nrf2 nuclear translocation and upregulation of antioxidant proteins, reducing ROS and lipid peroxidation.
  • Peripheral Nerve Injury:
    • Pinostrobin accelerates recovery in a rat model of sciatic nerve injury by decreasing oxidative stress levels, promoting axonal regeneration, and increasing the expression of p-ERK1/2.

Conclusion:

Pinostrobin’s protective effects extend beyond its known pharmacological properties, encompassing various organs and systems. From skin protection to neuroprotection, pinostrobin demonstrates a wide range of applications, making it a promising candidate for therapeutic development across multiple medical domains. Continued research into its specific mechanisms and clinical applications will likely unveil further potential therapeutic uses for this multifaceted compound. This comprehensive overview aims to provide a reference for researchers and clinicians exploring the diverse applications of pinostrobin in organ protection and neurological disorders.


reference link : https://journals.sagepub.com/doi/full/10.1177/1934578X231215934

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