Modulating the antibacterial effect of the existing antibiotics along with repurposing drug metformin.

Owing to the extensive prevalence of resistant bacteria to numerous antibiotic classes, antimicrobial resistance (AMR) poses a well-known hazard to world health. As an alternate approach in the field of antimicrobial drug discovery, repurposing the available medications which are also called antibiotic resistance breakers has been pursued for the treatment of infections with antimicrobial resistance pathogens. In this study, we used Haloperidol, Metformin and Hydroxychloroquine as repurposing drugs in in vitro (Antibacterial Antibiotic Sensitivity Test and Minimum Inhibitory Concentration-MIC) and in vivo (Shigellosis in Swiss albino mice) tests in combination with traditional antibiotics (Oxytetracycline, Erythromycin, Doxycycline, Gentamicin, Ampicillin, Chloramphenicol, and Penicillin) against a group of AMR resistance bacteria (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Shigella boydii). After observing the results of the conducted in vitro experiments we studied the effects of the above non antibiotic drugs in combination with the said antibiotics. As an repurposing adjuvant antibiotic drug, Metformin exhibited noteworthy activity in almost all in vitro, in vivo and in silico tests (Zone of inhibition for 30 to 43 mm for E.coli in combination with Doxycycline; MIC value decreased 50 µM to 0.781 µM with Doxycycline on S. boydii).In rodents Doxycycline and Metformin showed prominent against Shigellosis in White blood cell count (6.47 ± 0.152 thousand/mm3) and Erythrocyte sedimentation rate (10.5 ± 1.73 mm/hr). Our findings indicated that Metformin and Doxycycline combination has a crucial impact on Shigellosis. The molecular docking study was performed targeting the Acriflavine resistance protein B (AcrB) (PDB ID: 4CDI) and MexA protein (PDB ID: 6IOK) protein with Metformin (met8) drug which showed the highest binding energy with - 6.4 kcal/mol and - 5.5 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period. This study suggest Metformin and other experimented drugs can be used as adjuvants boost up antibiosis but further study is needed to find out the safety and efficacy of this non-antibiotic drug as potent antibiotic adjuvant.

Therapeutic and Mechanistic Approaches of Tridax Procumbens Flavonoids for the Treatment of Osteoporosis.

Homeostasis of bone is closely regulated by the balanced activities between the bone resorbing activity of osteoclast cells and bone-forming ability of osteoblast cells. Multinucleated osteoclasts degrade bone matrix and involve in the dynamic bone remodelling in coordination with osteoblasts. Disruption of this regulatory balance between these cells or any imbalance in bone remodelling caused by a higher rate of resorption over construction of bone results in a decrease of bone matrix including bone mineral density (BMD). These osteoclast-dominant effects result in a higher risk of bone crack and joint demolition in several bone-related diseases, including osteoporosis and rheumatoid arthritis (RA). Tridax procumbens is a very interesting perennial plant and its secondary metabolites called here T. procumbens flavonoids (TPFs) are well-known phytochemical agents owing to various therapeutic practices such as anti-inflammatory, anti-anaemic and anti-diabetic actions. This review designed to focus the systematic convention concerning the medicinal property and mechanism of actions of TPFs for the management of bone-related diseases. Based on the current literature, the review offers evidence-based information of TPFs for basic researchers and clinicians for the prevention and treatment of bone related diseases, including osteoporosis. It also emphasizes the medical significance for more research to comprehend the cellular signalling pathways of TPFs for the regulation of bone remodelling and discusses the possible promising ethnobotanical resource that can convey the preclinical and clinical clues to develop the next generation therapeutic agents for the treatment of bonerelated disorders.

Tridax procumbens flavonoids: a prospective bioactive compound increased osteoblast differentiation and trabecular bone formation.

BACKGROUND: The Tridax procumbens extracts (TPE) are known for their ethno-medicinal properties to increase osteogenic functioning in mesenchymal stem cells. Recently, we found that the T. procumbens flavonoids (TPF) significantly suppressed the RANKL-induced osteoclasts differentiation and bone resorption. The TPF also promoted osteoblasts differentiation and bone formation demonstrated by increasing bone formation markers in cultured mouse primary osteoblasts. However, the effects of the TPF on in vivo bone formation remain unclear. In this study, we investigated the effects of the TPF on in vivo bone formation, injected the TPF (20 mg/kg) twice a day in the low calcium diet mice and killed them after 21 day. Radiographic and histomorphometric analyses were performed on the dissected bones to determine the anabolic effects of the TPF. RESULTS: Bone mineral density and bone mineral content of the TPF-treated mice were significantly increased compared to the control mice. Bone formation-related indices like osteoblast number, osteoblast surface, bone volume, mineralizing surface, mineral apposition rate and bone formation rate were significantly increased in the TPF-treated mice compared to the control mice. CONCLUSION: Our findings point towards the stimulation of bone formation by TPF, suggested that the TPF could be a potential natural anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Tridax procumbens flavonoids: a prospective bioactive compound increased osteoblast differentiation and trabecular bone formation

BACKGROUND: The Tridax procumbens extracts (TPE) are known for their ethno-medicinal properties to increase osteogenic functioning in mesenchymal stem cells. Recently, we found that the T. procumbens flavonoids (TPF) significantly suppressed the RANKL-induced osteoclasts differentiation and bone resorption. The TPF also promoted osteoblasts differentiation and bone formation demonstrated by increasing bone formation markers in cultured mouse primary osteoblasts. However, the effects of the TPF on in vivo bone formation remain unclear. In this study, we investigated the effects of the TPF on in vivo bone formation, injected the TPF (20 mg/kg) twice a day in the low calcium diet mice and killed them after 21 day. Radiographic and histomorphometric analyses were performed on the dissected bones to determine the anabolic effects of the TPF. RESULTS: Bone mineral density and bone mineral content of the TPF-treated mice were significantly increased compared to the control mice. Bone formation-related indices like osteoblast number, osteoblast surface, bone volume, mineralizing surface, mineral apposition rate and bone formation rate were significantly increased in the TPF-treated mice compared to the control mice. CONCLUSION: Our findings point towards the stimulation of bone formation by TPF, suggested that the TPF could be a potential natural anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation.

BACKGROUND: Tridax procumbens flavonoids (TPFs) are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts. RESULTS: TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs) including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2. CONCLUSION: Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation

BACKGROUND: Tridaxprocumbens flavonoids (TPFs) are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts. RESULTS: TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs) including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2. CONCLUSION: Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Pesticidal and pest repellency activities of rhizomes of Drynaria quercifolia (J. Smith) against Tribolium castaneum (Herbst).

BACKGROUND: Tribolium castaneum (Herbst) is a harmful pest of stored grain and flour-based products in tropical and subtropical region. In the present study, rhizome of Drynaria quercifolia (J. Smith) was evaluated for pesticidal and pest repellency activities against T. castaneum, using surface film method and filter paper disc method, respectively. In addition, activity of the isolated compound 3,4-dihydroxybenzoic acid was evaluated against the pest. RESULTS: Chloroform soluble fraction of ethanol extract of rhizome of D. quercifolia showed significant pesticidal activity at doses 0.88 to 1.77 mg/cm(2) and significant pest repellency activity at doses 0.94 to 0.23 mg/cm(2). No pesticidal and pest repellency activity was found for petroleum ether, ethyl acetate and methanol soluble fractions of ethanol extract as well as for 3,4-dihydroxybenzoic acid. CONCLUSION: Considering our findings it can be concluded that chloroform soluble fraction of rhizome of D. quercifolia is useful in controlling T. castaneum of stored grain and flour-based products.

Pesticidal and pest repellency activities of rhizomes of Drynaria quercifolia (J. Smith) against Tribolium castaneum (Herbst)

BACKGROUND: Tribolium castaneum (Herbst) is a harmful pest of stored grain and flour-based products in tropical and subtropical region. In the present study, rhizome of Drynaria quercifolia (J. Smith) was evaluated for pesticidal and pest repellency activities against T. castaneum, using surface film method and filter paper disc method, respectively. In addition, activity of the isolated compound 3,4-dihydroxybenzoic acid was evaluated against the pest. RESULTS: Chloroform soluble fraction of ethanol extract of rhizome of D. quercifolia showed significant pesticidal activity at doses 0.88 to 1.77 mg/cm² and significant pest repellency activity at doses 0.94 to 0.23 mg/cm². No pesticidal and pest repellency activity was found for petroleum ether, ethyl acetate and methanol soluble fractions of ethanol extract as well as for 3,4-dihydroxybenzoic acid. CONCLUSION: Considering our findings it can be concluded that chloroform soluble fraction of rhizome of D. quercifoliais useful in controlling T. castaneum of stored grain and flour-based products.