Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway

Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as nutraceutical to combat inflammation, virus and obesity. Parkinson’s Disease (PD) is a...

Utilizing the Crosstalk Among Minocycline, Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized) and Vitamin D as a Potent Quadrate Therapy for treating coinfection with Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study

Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. TB is considered a disease caused by a bacterium—Mycobacterium tuberculosis—that usually attacks the lungs, but can attack any part of the body. But TB has a worrisome connection to the novel coronavirus.. Both diseases are airborne and spread when people cough or sneeze. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden, stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge. Recently it was showed that hospitalized patients with Tuberculosis are more susceptible to COVID-19 infection and complication. Furthermore, hospitalized patients with MDR-TB are increasingly vulnerable to COVID-19 complications than patients with non-resistant tuberculosis.. For someone with latent TB, contracting COVID-19 could activate the bacterium, potentially leading to an accelerated and more severe form of the disease WHO estimates that these COVID-19 related disruptions in access to TB care could cause an additional half a million TB deaths. Older age, especially >65 years, may be a risk factor for death from COVID-TB, consistent with previous findings indicating that the mortality rate from COVID-19 increases exponentially with age. Thus, the elderly should be the primary focus of both COVID-19 and COVID-TB mitigation efforts due to its much higher mortality risk in that group. COVID-TB patients had a much higher rate of comorbidities than COVID-19 patients At present, evidence suggests that the main transmission route of both COVID-19 and TB is via respiratory droplets, and their main target are the lungs, which can lead to a worse outcome among COVID-19 and TB coinfection patients (aptly abbreviated COVID-TB). As a result, coinfections with common viral and bacterial (COVID-TB) pathogens among hospitalized patients are a severe concern that will likely worsen patient outcomes and pose a real challenge for treating those patients.ConclusionsNew drug discovery could require several years with no guarantee but repurposing established drugs may be useful to treat confection with COVID-19 and Nonresistant Strains of Mycobacterium tuberculosis: or resistant Strains of Mycobacterium tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline and vitamin D as a novel quadrate therapy against Multidrug-resistant TB and COVID-19 coinfection.

Chicoric acid prevents neurodegeneration via microbiota-gut-brain axis in a mouse Parkinson's disease model

It is determined that microbiota-gut-brain axis is involved in the pathogenesis of Parkinson's Disease (PD) and may be the potential target for developing the therapeutic treatments for PD. Chicoric acid (CA) is a kind of natural polyphenolic acid compounds which are recognized as promising agents against neurodegenerative disease. Here, we investigated the influence of CA on microbiota-gut-brain axis in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mice. The results demonstrated that oral pretreatments of CA significantly prevented the MPTP-indued motor disorders, death of nigrostriatal dopaminergic neurons and reduction in striatal neurotrophins. Sequencing results of 16S rRNA indicated the microbial dysbiosis occurred in MPTP mice, whereas CA exerted a remarkable impact on microbial diversity and microbiota compositions, as well as SCFAs production. Besides, CA pretreatment alleviated gliosis-mediated neuroinflammation and gut inflammation by suppressing TLR4/MyD88/NF-?5;B signaling cascade, along with preventing the colonic hyperpermeability. To conclude, CA prevented MPTP-induced neuroinflammation and neuronal degenerative processes through signaling multiple pathways of microbiota-gut-brain axis.

Versatility in acyltransferase activity completes chicoric acid biosynthesis in purple coneflower

Purple coneflower (Echinacea purpurea (L.) Moench) is a popular native North American herbal plant. Its major bioactive compound, chicoric acid, is reported to have various potential physiological functions, but little is known about its biosynthesis. Here, taking an activity-guided approach, we identify two cytosolic BAHD acyltransferases that form two intermediates, caftaric acid and chlorogenic acid. Surprisingly, a unique serine carboxypeptidase-like acyltransferase uses chlorogenic acid as its acyl donor and caftaric acid as its acyl acceptor to produce chicoric acid in vacuoles, which has evolved its acyl donor specificity from the better-known 1-O-β-D-glucose esters typical for this specific type of acyltransferase to chlorogenic acid. This unusual pathway seems unique to Echinacea species suggesting convergent evolution of chicoric acid biosynthesis. Using these identified acyltransferases, we have reconstituted chicoric acid biosynthesis in tobacco. Our results emphasize the flexibility of acyltransferases and their roles in the evolution of specialized metabolism in plants.

Chicoric acid alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in human lung A549 epithelial cells

To investigate the effects and potential mechanisms of chicoric acid (CA) on LPS-induced inflammatory response in A549 cells. 0–800 μM CA was added to A549 cells to determine the toxicity of CA using MTT assay. Then, 2 μg/mL LPS and 50 μM CA were simultaneously added to A549 cells to investigate the effects of CA. In order to investigate the effects of miR-130a-3p and IGF-1 on LPS-induced A549 cells, cells were infected with inhibitor of miR-130a-3p and si RNA IGF-1. The levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α were measured by real-time RT-PCR and enzyme-linked immunosorbent (ELISA) assay. The IGF-1 pathway and NF-κB expression were measured using immunoblot assay. Moreover, a luciferase activity assay was used to indicate the binding site of miR-130a-3p on the 3′UTR of IGF-1. 0–50 μM CA had no toxicity on A549 cells. Thus, we chose 50 μM CA for the following study. CA attenuated the inflammatory response by LPS through decreasing IL-1β, IL-6, and TNF-α levels and increasing IGF-1/IGF-1R expression. Inhibition of miR-130a-3p reduced the inflammatory response and restored IGF-1/IGF-1R pathway induced by LPS. Furthermore, luciferase activity results indicated that miR-130a-3p directly targeted IGF-1 to regulate inflammatory response. CA alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in A549 cells.