Fermented Polyherbal Formulation Ameliorates the Severity of Acute Multiple Antibiotics-Resistant Pseudomonas aeruginosa-Infected Burn Wound in a Rat Burn Model

Article

Author: Chakraborty, Ranadhir ; Sen, Subhajit ; Chakraborty, Subhanil ; Das, Arghya

Pseudomonas aeruginosa, a Gram-negative opportunistic bacterium, has emerged as a cause of life-threatening infections in burn wounds. Current therapeutic approaches through wound dressings and systemic medicines are far from satisfactory; resistance to more than two antibiotics shown by pathogens contributes to failures of therapy causing mortality. This animal study was conducted to check the efficacy of one Ayurveda-based fermented polyherbal preparation (AP 01) against multiple antibiotics-resistant (MAR) P. aeruginosa HW01-infected rat burn wounds. AP-01 was applied on artificially infected burn wound on a rat model infected with MAR P. aeruginosa to register the healing effects in terms of reduction in residual wound area percentage, the presence of C-reactive protein in blood, and the presence of viable bacteria colony. Topical application with conventional antibiotics served as a positive control. The polyherbal preparation had reduced the infected residual burn wound area at 40.63% ± 0.69 from the initial burn wound area within two weeks after a single intervention, whereas residual burn wound area remained much higher in the case of animals left untreated and in the case of the animals treated with control drug. Restoration to the normalcy of serum C-reactive protein level was also achieved earlier in the case of polyherbal AP-01-treated groups than in other groups. Fermented formulations using components of AP-01 singly or in different combinations had never been tested earlier for topical application in infected burn wound. The formulation of AP-01 was found superior in terms of the rate of healing and control of infection by MAR P. aeruginosa strains in burn wounds in rat models.

01 Apr 2024·International Journal of Biological Macromolecules

Effects of almond (Armeniaca Sibirica L. Lam) polysaccharides on gut microbiota and anti-inflammatory effects on LPS-induced RAW264.7 cells

Article

Author: Yue, Xiqing ; Li, Yingshuo ; Pi, Yuzhen ; Peng, Yanqi

The aim of this study was to investigate the prebiotic properties of the almond polysaccharide AP-1 on intestinal microorganisms by using an in vitro fecal fermentation method and its anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW264.7 cells. The results showed that during the in vitro fermentation of AP-1, the pH value of the fermentation broth decreased obviously, while the concentration of short-chain fatty acids (SCFAs) increased significantly, especially acetic acid and butyric acid. In genus level, the number of Clostridium and Megamonas increased markedly in the AP-1 group after 24 h of fermentation. After 48 h of fermentation, there was a noticeable increase in the number of beneficial genera Lactobacillaceae and Bifidobacteriaceae, and a considerable decrease in the number of pro-inflammatory genera. In addition, we found that AP-1 had no toxic effect on RAW264.7 cells. In the LPS-induced inflammation model of RAW264.7 cells, AP-1 could effectively inhibit the release of NO, regulate the level of reactive oxides (ROS), and effectively down-regulate the mRNA expression of TNF-α, IL-1β, IL-6 and iNOS. In conclusion, the almond polysaccharide AP-1 may be a functional active substance aimed at promoting intestinal health and exerting anti-inflammatory effects.

01 Jan 2024·European Journal of Medicinal Chemistry

Highly potent dual-targeting angiotensin-converting enzyme 2 (ACE2) and Neuropilin-1 (NRP1) peptides: A promising broad-spectrum therapeutic strategy against SARS-CoV-2 infection

Article

Author: Jiang, Su ; Mei, Shuang ; Yang, Peng ; Niu, Miao-Miao ; Xue, Lu ; Wang, Yuting ; Jing, Han ; Zhang, Yan ; Li, Jindong ; Zou, Yunting ; Yuan, Kai

The efficacy of approved vaccines has been diminishing due to the increasing advent of SARS-CoV-2 variants with diverse mutations that favor sneak entry. Nonetheless, these variants recognize the conservative host receptors angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) for entry, rendering the dual blockade of ACE2 and NRP1 an advantageous pan-inhibition strategy. Here, we identified a highly potent dual-targeting peptide AP-1 using structure-based virtual screening protocol. AP-1 had nanoscale binding affinities for ACE2 (K_d = 6.1 ± 0.2 nM) and NRP1 (K_d = 13.4 ± 1.2 nM) and approximately 102- and 8-fold stronger than positive inhibitors S_471-503 and NMTP-5, respectively. Further evidence in pseudovirus cell infection and cytotoxicity assays demonstrated that AP-1 exhibited remarkable entry inhibition of variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. Together, our findings suggest that AP-1 with dual-targeting ACE2/NRP1 efficacy could be a promising broad-spectrum agent for treating SARS-CoV-2 emerging VOCs.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Preclinical	FR	Apmonia Therapeutics SAS	09 Aug 2022
Glioblastoma	Preclinical	FR	Apmonia Therapeutics SAS	09 Aug 2022
Ovarian Cancer	Preclinical	FR	Apmonia Therapeutics SAS	09 Aug 2022
Pancreatic Cancer	Preclinical	FR	Apmonia Therapeutics SAS	09 Aug 2022

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