Herbs And Phytochemicals: Study Uncovers Antiviral, Anti-Inflammatory, Anticancer And Neuroprotective Effects Of Pinostrobin From Carya Cathayensis

Herbs And Phytochemicals: In the realm of traditional Chinese medicine, the quest for potent therapeutic compounds has led researchers to uncover the multifaceted benefits of the phytochemical pinostrobin, a flavonoid compound prominently found in herbs like Carya cathayensis leaves, Boesenbergia rotunda, and propolis. With a molecular weight of 270.28 daltons, pinostrobin stands out for its remarkable pharmacological activities, coupled with a commendable safety profile. This Herbs And Phytochemicals article embarks on a comprehensive exploration of pinostrobin, delving into its antiviral, anti-inflammatory, anticancer, and neuroprotective attributes, with a keen focus on recent research findings.


Carya-Cathayensis 

Understanding Pinostrobin
Pinostrobin, chemically known as C16H14O4, is a small flavonoid compound characterized by its wide distribution in various traditional Chinese herbs. Metabolized mainly by glucuronidation, pinostrobin exhibits higher concentrations in the liver and gastrointestinal tract than in other tissues, underscoring its potential influence on various physiological processes.
 
Antiviral Prowess
Pinostrobin's antiviral effects have been a subject of significant research. In the context of herpes simplex virus type 1 (HSV-1), a prevalent infection affecting approximately 60% of individuals under 50 globally, pinostrobin demonstrates inhibitory actions. By binding to the glycoprotein gD of HSV-1, it disrupts viral adsorption and impedes replication.
 
The ongoing global battle against respiratory viruses such as SARS-CoV-2 and human coronavirus OC43 finds a potential ally in pinostrobin. Through hydrophobic bonds, pinostrobin binds to the main protease of SARS-CoV-2, inhibiting its activity and curtailing viral proliferation.
 
Additionally, it showcases efficacy against HCoV-OC43 by modulating the AHR/CYP1A1 pathway and increasing prostaglandin E2 (PGE2) levels.
 
Antibacterial, Antifungal, and Antiparasitic Excellence
Pinostrobin's reach extends beyond viral infections to combat a variety of bacterial, fungal, and parasitic challenges. In bacterial inhibition, it has shown efficacy against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus, and the notorious Helicobacter pylori. Its antibiofilm properties and reduction of efflux pump activity underscore its potential in combating bacterial resistance.
 
Fungal infections face resistance from pinostrobin as well, with its ability to inhibit the growth of yeast and reduce the activity of protein kinase Swe1 in a Ca2+-dependent manner.
 
Antiparasitic potential is evident in pinostrobin's effectiveness against cysticercosis, Giardia, Leishmania, and Trypanosoma americanum. By causing glycogen granule and vacuole accumulation, pinostrobin emerges as a promising agent in the fight against parasitic infections.
 
Eff ects on Lipid Metabolism
The influence of pinostrobin on lipid metabolism marks a significant stride in its therapeutic potential. Altering lipid metabolomics, especially in folate and arachidonic acid metabolism, pinostrobin showcases its prowess in reducing triglyceride levels and inhibiting adipogenic differentiation.
 
Key transcription factors associated with adipogenesis, namely peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), fall under pinostrobin's regulatory influence. By inhibiting the expression of these genes, pinostrobin curtails lipid droplet formation and adipogenic differentiation, with the MAPK and AKT signaling pathways coming into play.
 
Addressing the scourge of low-density lipoprotein cholesterol (LDLC), a prominent risk factor for atherosclerosis and certain cancers, pinostrobin's interaction with proprotein convertase subtilisin/kexin type 9 (PCSK9) is noteworthy. By promoting competitive binding of FoxO3a to the PCSK9 promoter, pinostrobin reduces PCSK9 transcription, enhancing LDL receptor (LDLR) activity and facilitating LDLC uptake.
 
Uric Acid Reduction
Hyperuricemia-associated conditions, such as gout, find a potential remedy in pinostrobin. Acting on xanthine oxidase (XOD), a key player in uric acid production, pinostrobin effectively reduces serum uric acid levels without adversely affecting liver function or normal uric acid levels.
 
Anticancer Marvel
The realm of cancer research reveals pinostrobin's impressive anticancer potential across various cancer cell lines, including HT-29, HeLa, A549, and PC-3 cells. Molecular docking analyses illuminate pinostrobin's binding affinity to critical cancer-promoting molecules such as epidermal growth factor receptor (EGFR), tyrosine-protein kinase (JAK-2), and DNA topoisomerase I (TOP1).

In addition to mutagenic inhibition, pinostrobin emerges as a formidable adversary against cancer stem cells, hindering proliferation and inducing apoptosis through reactive oxygen species (ROS)-mediated mitochondrial damage.
 
Metastasis and invasion, primary contributors to cancer recurrence and therapy resistance, face a roadblock in pinostrobin's ability to inhibit breast cancer cell migration. Notably, it also overcomes multidrug resistance in cancer cells by inhibiting P-glycoprotein (Pgp) activity without impacting its expression.

The potential for leukemia treatment with pinostrobin is compelling. Its multifaceted approach includes the inhibition of miR-410-5p, promotion of β-catenin degradation, and induction of apoptosis in acute leukemia cells.
 
Anti-Inflammatory Efficacy
Pinostrobin's anti-inflammatory prowess unfolds across various contexts, demonstrating a protective shield against gastric mucosal injury, peptic ulcers, and inflammatory responses induced by alcohol. Its direct binding to toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD2) complex inhibits the LPS/NF-κB-induced inflammatory cascade in macrophages.
 
Extensive documentation supports pinostrobin's anti-inflammatory effects, with reductions in proinflammatory factors such as IL-6, IL-1β, TNF-α, and COX-2 observed in different cell types and rat inflammation models.
 
Multiple Organ Protection
Beyond its individual therapeutic facets, pinostrobin emerges as a guardian of multiple organs, owing to its antioxidant and anti-inflammatory properties.

-Liver: Protection against thioacetamide-induced liver injury highlights pinostrobin's potential in preventing liver cirrhosis and fibrosis. Its actions include increasing antioxidant enzyme activities, reducing oxidative stress, and modulating inflammatory cytokines.
 
-Kidney: In studies with Type I Mardin Darby Canine Kidney (MDCK) cells, pinostrobin exhibits a marked reduction in cyst formation and growth. By inhibiting cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride secretion and reducing ERK phosphorylation, pinostrobin shows promise in addressing polycystic kidney conditions.
 
-Bone: Pinostrobin emerges as a promoter of bone health by countering the adverse effects of reactive oxygen species (ROS) on osteoblast function. Its role in modulating bone formation and resorption positions it as a potential adjunct in managing osteoporosis.
 
-Skin: Ultraviolet radiation-induced skin damage faces mitigation with pinostrobin, which ameliorates oxidative stress and inflammation. This makes it a potential candidate for skincare formulations and sunscreens.
 
-Reproductive System: Reproductive health benefits from pinostrobin's ability to protect ovarian granulosa cells from oxidative stress-induced apoptosis, offering insights into fertility preservation and reproductive medicine.
 
-Stomach: Gastric mucosal protection is one of pinostrobin's noted attributes, demonstrated through its attenuation of ethanol-induced gastric injury. This protective effect is attributed to the inhibition of oxidative stress, preservation of antioxidant enzyme activities, and reduction of inflammatory cytokines.
 
-Nerves: The nervous system finds a shield in pinostrobin's neuroprotective effects. Through its antioxidant actions, it combats oxidative stress-induced neuronal damage and holds promise in addressing neurodegenerative diseases.
 
-Neuroprotective Brilliance
Pinostrobin's neuroprotective effects extend to various neurological conditions, including peripheral nerve injury, Alzheimer's disease, and Parkinson's disease.

In models of peripheral nerve injury, pinostrobin facilitates nerve regeneration by promoting the expression of growth-associated protein 43 (GAP-43), enhancing axonal elongation, and mitigating oxidative stress. These actions position it as a potential therapeutic agent for nerve injury repair.
 
The fight against Alzheimer's disease sees pinostrobin intervening at multiple levels. By inhibiting β-amyloid (Aβ) aggregation, reducing tau hyperphosphorylation, and suppressing neuroinflammation, pinostrobin holds promise in slowing disease progression.
 
Parkinson's disease, characterized by the loss of dopaminergic neurons, faces a potential ally in pinostrobin. By attenuating oxidative stress, reducing neuroinflammation, and preserving mitochondrial function, pinostrobin showcases neuroprotective effects in models of Parkinson's disease.
 
Conclusion
The journey through pinostrobin's multifaceted therapeutic potential unravels a remarkable story of a natural compound with diverse applications. From its roots in traditional Chinese herbs to the forefront of modern medicine, pinostrobin emerges as a versatile therapeutic agent with promising implications in antiviral treatments, cancer therapy, neuroprotection, and organ health.
 
The road ahead involves continued exploration of pinostrobin's mechanisms of action, optimization of formulations, and rigorous clinical testing. As researchers and medical professionals delve deeper into the intricacies of pinostrobin, its promise as a transformative agent in regenerative medicine and disease management becomes increasingly evident.
 
As we stand on the precipice of a new era in healthcare, pinostrobin beckons as a beacon of hope and innovation. The collaborative efforts of researchers, clinicians, and pharmaceutical developers hold the key to unlocking the full therapeutic potential of this extraordinary compound, paving the way for a future where pinostrobin plays a pivotal role in enhancing human health and well-being.
 
The study findings were published in the peer reviewed journal: Natural Products Communications. (Sage Journals).
https://journals.sagepub.com/doi/full/10.1177/1934578X231215934
 
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