IRF3 function and immunological gaps in sepsis.

Lipopolysaccharide (LPS) induces potent cell activation via Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD-2), often leading to septic death and cytokine storm. TLR4 signaling is diverted to the classical acute innate immune, inflammation-driving pathway in conjunction with the classical NF-κB pivot of MyD88, leading to epigenetic linkage shifts in nuclear pro-inflammatory transcription and chromatin structure-function; in addition, TLR4 signaling to the TIR domain-containing adapter-induced IFN-ß (TRIF) apparatus and to nuclear pivots that signal the association of interferons alpha and beta (IFN-α and IFN-ß) with acute inflammation, often coupled with oxidants favor inhibition or resistance to tissue injury. Although the immune response to LPS, which causes sepsis, has been clarified in this manner, there are still many current gaps in sepsis immunology to reduce mortality. Recently, selective agonists and inhibitors of LPS signals have been reported, and there are scattered reports on LPS tolerance and control of sepsis development. In particular, IRF3 signaling has been reported to be involved not only in sepsis but also in increased pathogen clearance associated with changes in the gut microbiota. Here, we summarize the LPS recognition system, main findings related to the IRF3, and finally immunological gaps in sepsis.

Sakuranetin and its therapeutic potentials - a comprehensive review.

Sakuranetin (SKN), a naturally derived 7-O-methylated flavonoid, was first identified in the bark of the cherry tree (Prunus spp.) as an aglycone of sakuranin and then purified from the bark of Prunus puddum. It was later reported in many other plants including Artemisia campestris, Boesenbergia pandurata, Baccharis spp., Betula spp., Juglans spp., and Rhus spp. In plants, it functions as a phytoalexin synthesized from its precursor naringenin and is the only known phenolic phytoalexin in rice, which is released in response to different abiotic and biotic stresses such as UV-irradiation, jasmonic acid, cupric chloride, L-methionine, and the phytotoxin coronatine. Till date, SKN has been widely reported for its diverse pharmacological benefits including antioxidant, anti-inflammatory, antimycobacterial, antiviral, antifungal, antileishmanial, antitrypanosomal, glucose uptake stimulation, neuroprotective, antimelanogenic, and antitumor properties. Its pharmacokinetics and toxicological properties have been poorly understood, thus warranting further evaluation together with exploring other pharmacological properties such as antidiabetic, neuroprotective, and antinociceptive effects. Besides, in vivo studies or clinical investigations can be done for proving its effects as antioxidant and anti-inflammatory, antimelanogenic, and antitumor agent. This review summarizes all the reported investigations with SKN for its health-beneficial roles and can be used as a guideline for future studies.

A review on chemistry, source and therapeutic potential of lambertianic acid.

Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

Artepillin C: A comprehensive review of its chemistry, bioavailability, and pharmacological properties.

Artepillin C (ARC), a prenylated derivative of p-coumaric acid, is one of the major phenolic compounds found in Brazilian green propolis (BGP) and its botanical source Baccharis dracunculifolia. Numerous studies on ARC show that its beneficial health effects correlate with the health effects of both BGP and B. dracunculifolia. Its wide range of pharmacological benefits include antioxidant, antimicrobial, anti-inflammatory, anti-diabetic, neuroprotective, gastroprotective, immunomodulatory, and anti-cancer effects. Most studies have focused on anti-oxidation, inflammation, diabetic, and cancers using both in vitro and in vivo approaches. Mechanisms underlying anti-cancer properties of ARC are apoptosis induction, cell cycle arrest, and the inhibition of p21-activated kinase 1 (PAK1), a protein characterized in many human diseases/disorders including COVID-19 infection. Therefore, further pre-clinical and clinical studies with ARC are necessary to explore its potential as intervention for a wide variety of diseases including the recent pandemic coronaviral infection. This review summarizes the comprehensive data on the pharmacological effects of ARC and could be a guideline for its future study and therapeutic usage.