Microbiological acceptance criteria, specifications of herbal drugs and herbal drug preparations in various pharmacopoeias: a global scenario.

PURPOSE: A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region. METHOD: In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated. RESULTS: It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination. CONCLUSION: From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Cyperus rotundus L.: Invasive weed plant with insecticidal potential against Aphis craccivora Koch and Planococcus lilacinus (Cockerell).

Cyperus rotundus L. is a widely distributed invasive weed plant with vast traditional medicinal uses. Herein, the methanolic root extract of C. rotundus and its fractions (n-hexane, chloroform, n-butanol, and aqueous) were evaluated for insecticidal activity against nymphs of Aphis craccivora Koch and crawlers of Planococcus lilacinus (Cockerell) to find promising lead (s). In contact topical assay, among extract/fractions, n-hexane fraction exhibited more toxicity against A. craccivora (LD50 = 1.12 µg/insect) and P. lilacinus (LD50 = 0.94 µg/insect). The chemical analysis of n-hexane fraction revealed a volatile composition similar to that of the essential oil (EO) of C. rotundus roots. Hence, EO was extracted using water and deep eutectic solvents (DESs) as cosolvent, which revealed enhancement in EO yield (from 0.28 to 0.46% w/w) on implementing DESs. A total of 35 diverse volatile metabolites were identified in all EO samples, accounting for 85.0 to 91.8% of chemical composition, having cyperotundone, cyperene mustakone, isolongifolen-5-one, boronia butenal as major constituents. The EO obtained with DES-7 [choline chloride: ethylene glycol (1:4)] and DES-6 [choline chloride: lactic acid (1:3)] were found effective against A. craccivora (LD50 = 0.62-0.87 µg/insect) and P. lilacinus (LD50= 0.59-0.67 µg/insect) after 96 h. NMR analysis of EO revealed cyperotundone as a major compound, which was isolated along with cyperene and cyperene epoxide. All the molecules were found effective against P. lilacinus, whereas against A. craccivora cyperotundone, cyperene and cyperene epoxide showed promising toxicity (LD50 = 0.74-0.86 µg/insect). Extract/fractions, EO, and isolated molecules showed a significant reproductive inhibition rate of A. craccivora at higher concentrations. All the tested concentrations of cyperotundone showed significant inhibition of acetylcholinesterase (AChE) and glutathione-S-transferase (GST) in A. craccivora and P. lilacinus. Based upon the present study, C. rotundus can be recommended to control targeted insects in the greenhouse/field conditions after performing bio-efficacy and phytotoxicity studies.

Antibiotic Potentiation Through Phytochemical-Based Efflux Pump Inhibitors to Combat Multidrug Resistance Bacteria.

BACKGROUND: Antimicrobial resistance development poses a significant danger to the efficacy of antibiotics, which were once believed to be the most efficient method for treating infections caused by bacteria. Antimicrobial resistance typically involves various mechanisms, such as drug inactivation or modification, drug target modification, drug uptake restriction, and drug efflux, resulting in decreased antibiotic concentrations within the cell. Antimicrobial resistance has been associated with efflux Pumps, known for their capacity to expel different antibiotics from the cell non-specifically. This makes EPs fascinating targets for creating drugs to combat antimicrobial resistance (AMR). The varied structures of secondary metabolites (phytomolecules) found in plants have positioned them as a promising reservoir of efflux pump inhibitors. These inhibitors act as modifiers of bacterial resistance and facilitate the reintroduction of antibiotics that have lost clinical effectiveness. Additionally, they may play a role in preventing the emergence of multidrug resistant strains. OBJECTIVE: The objective of this review article is to discuss the latest studies on plant-based efflux pump inhibitors such as terpenoids, alkaloids, flavonoids, glycosides, and tetralones. It highlighted their potential in enhancing the effectiveness of antibiotics and combating the development of multidrug resistance. strains. RESULTS: Efflux pump inhibitors (EPIs) derived from botanical sources, including compounds like lysergol, chanaoclavine, niazrin, 4-hydroxy-α-tetralone, ursolic acid, phytol, etc., as well as their partially synthesized forms, have shown significant potential as practical therapeutic approaches in addressing antimicrobial resistance caused by efflux pumps. Further, several phyto-molecules and their analogs demonstrated superior potential for reversing drug resistance, surpassing established agents like reserpine, niaziridin, etc. strains. CONCLUSION: This review found that while the phyto-molecules and their derivatives did not possess notable antimicrobial activity, their combination with established antibiotics significantly reduced their minimum inhibitory concentration (MIC). Specific molecules, such as chanaoclavine and niaziridin, exhibited noteworthy potential in reversing the effectiveness of drugs, resulting in a reduction of the MIC of tetracycline by up to 16 times against the tested strain of bacteria. These molecules inhibited the efflux pumps responsible for drug resistance and displayed a stronger affinity for membrane proteins. By employing powerful EPIs, these molecules can selectively target and obstruct drug efflux pumps. This targeted approach can significantly augment the strength and efficacy of older antibiotics against various drug resistant bacteria, given that active drug efflux poses a susceptibility for nearly all antibiotics.

Silane Coatings for Corrosion and Microbiologically Influenced Corrosion Resistance of Mild Steel: A Review.

Mild steel continues to be the most extensively used construction material in several industries and constructions. However, corrosion of mild steel in aggressive environments is a major concern. Under the tremendously increasing demand for improving the coatings strategies because of the environmental concerns due to some of the traditional coatings, silane pre-treatments have been emerging as one of the effective solutions, among other strategies. Different approaches, such as adding particles of metal oxide (such as SiO2, ZrO2, Al2O3, TiO2 and CeO2), incorporating plant extracts and impregnating 2D materials into the coatings, have been employed for durable corrosion resistance, including for mitigating enhanced corrosion due to the presence of bacteria. This review discusses the critical mechanistic features of silane coatings such as the role of hydrolysis and condensation in the bonding of silanes with metal surfaces. The factors that influence the performance of the silane coatings for corrosion resistance of mild steel are discussed. In particular, this review provides insight into silane coatings for mitigating microbiologically influenced corrosion (MIC) of mild steel.

Antiplasmodial diterpenoid alkaloid from Aconitum heterophyllum Wall. ex Royle: Isolation, characterization, and UHPLC-DAD based quantification.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum heterophyllum Wall. ex Royle is a traditionally important medicinal plant having numerous therapeutic actions as documented in Ayurveda. This plant is traditionally known for combating worm infestation, fever, respiratory tract disease, vomiting, diarrhoea, diabetes, skin disorders, anaemia, and joint disorders. Further, it has been used alone and in combination with other plants to prepare various anti-malarial formulations. However, there is no report on the assessment of its anti-plasmodial activity, and the metabolite(s) responsible for this activity. AIM OF THE STUDY: The main aim of this study was to conduct phytochemical investigation of A. heterophyllum roots for the preparation of extract, fractions, and isolation of pure molecules to identify active fractions/molecules responsible for the anti-plasmodial activity, and development of UHPLC-DAD based analytical method which can be used for the quantification of marker compounds in the extracts and fractions. MATERIALS AND METHODS: Hydroalcoholic extract (1:1 v/v) and fractions (n-hexane, chloroform, ethyl acetate, n-butanol, and water) were prepared from the dried powdered roots of A. heterophyllum. Fractions were further subjected to silica gel column chromatography to isolate pure specialized secondary metabolites from this plant. All extracts, fractions, and pure molecules were evaluated against the chloroquine resistant Pf INDO and chloroquine sensitive Pf3D7 strains in culture for calculating their IC50 values. UHPLC-DAD based analytical method was also developed for the first time for the quantification of marker compounds and quality assessment of this commercially important Himalayan medicinal plant. RESULTS: Phytochemical investigation of A. heterophyllum root led to the isolation of six specialized metabolites viz. 2-O-cinnamoyl hetisine (1), atisinium (2), 4-oxabicyclo [3.2.2] nona-1(7),5,8-triene (3), atisinium cinnamate (4), aconitic acid (5), and atisinium formate (6). Compound 1 is a new hetisine type diterpenoid alkaloid, compounds 4 and 6 are new counter ionic forms observed with atisinium ion, and compound 3 is being reported for the first time from this genus. Chloroform fraction was found to be the most active with IC50 (µg/mL) 1.01 (Pf INDO) and 1.32 (Pf3D7). The molecule 2-O-cinnamoyl hetisine (1), a new diterpenoid alkaloid isolated from chloroform fraction, showed promising antiplasmodial activities with IC50 (µM) 1.92 (Pf INDO) and 10.8 (Pf 3D7). The activity of chloroform fraction was further validated by the developed UHPLC-DAD based method as the quantity of 2-O-cinnamoyl hetisine (1) was higher in the chloroform fraction (≅200 mg/g) than in all other fractions (<7 mg/g). Atisinium (2) and 2-O-cinnamoyl hetisine (1) were found to be the main marker compounds of this plant based on quantity and antiplasmodial activity, respectively. CONCLUSION: This study provides the scientific rationale for the traditional use of this plant in treating malaria. Further, this study revealed that the anti-malarial potential of this plant might be due to the presence of diterpenoid alkaloids.

Antibacterial and membrane damaging activity of Livistona chinensis fruit extract.

Livistona chinensis is used in traditional Chinese medicine as an anticancer agent. Experimental studies have shown the antiproliferative and antiangiogenic properties of extracts of L. chinensis fruits and seeds. In the present study, qualitative phytochemical composition of L. chinensis fruits was investigated. We hypothesized that the presence of high concentration of phenolic compounds with astringent properties may result in bacterial cell death. Hence, antibacterial activity of an aqueous extract of L. chinensis fruits was investigated against Staphylococcus aureus. The antibacterial activity was attributed to DNA, enzyme and protein denaturing properties of the phenolic compounds present in the extract. The extract also resulted in increased membrane permeability. The antibacterial, DNA and enzyme denaturing and membrane damaging activity was limited to an acid-precipitable fraction of the extract and these effects were abrogated in presence of proteins. The membrane damaging activity of phenolic compounds was also observed in leucocytes. In conclusion, this study reported the antibacterial activity of the fruits of L. chinensis due to their high content of phenolic compounds.

The clinical benefits of tenofovir for simian immunodeficiency virus-infected macaques are larger than predicted by its effects on standard viral and immunologic parameters.

Previous studies have demonstrated that tenofovir (9-[2-(phosphonomethoxy)propyl]adenine; PMPA) treatment is usually very effective in suppressing viremia in macaques infected with simian immunodeficiency virus (SIV). The present study focuses on a subset of infant macaques that were chronically infected with highly virulent SIVmac251, and for which prolonged tenofovir treatment failed to significantly suppress viral RNA levels in plasma despite the presence of tenofovirsusceptible virus at the onset of therapy. While untreated animals with similarly high viremia developed fatal immunodeficiency within 3-6 months, these tenofovir-treated animals had significantly improved survival (up to 3.5 years). This clinical benefit occurred even in animals for which tenofovir had little or no effect on CD4 and CD8 lymphocyte counts and antibody responses to SIV and test antigens. Thus, the clinical benefits of tenofovir were larger than predicted by plasma viral RNA levels and other routine laboratory parameters.