Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic interventions in various diseases, including cancers. According to the framework of autophagy, the suppression or induction of autophagy can exert therapeutic properties through the promotion of cell death or cell survival, which are the two main events targeted by cancer therapies. Remarkably, natural products have attracted attention in the anticancer drug discovery field, because they are biologically friendly and have potential therapeutic effects. In this review, we summarize the up-to-date knowledge regarding natural products that can modulate autophagy in various cancers. These findings will provide a new position to exploit more natural compounds as potential novel anticancer drugs and will lead to a better understanding of molecular pathways by targeting the various autophagy stages of upcoming cancer therapeutics

Antibiotic resistant microencapsulated probiotics synergistically preserved orange juice

BACKGROUND: In contemporary medicine, the utilization of various dosage forms of probiotics is increasing both for the treatment of human and animal diseases in Bangladesh. A number of imported pharmaceutical probiotic preparations are available in the local markets at present without justification the scientific information of viability. This study was, therefore, designed to explore the viability of commercial probiotics as well as recommend the consumers for the better products in term of viability. Since probiotics preserved foods have expanded in acceptance, popularity and compliance, the goal of this research was also to investigate the combination effects of lactic acid bacteria (LAB) on development of functional foods like orange juice (OJ). METHODS: Here, we screened five commercially available pharmaceutical probiotic products for rejuvenation and identification of LAB and associated resistance against different classes of antibiotics. Finally, the isolated LAB were microencapsulated and compared with free form of bacteria for biopreservation of OJ. RESULTS: We observed an inconsistency between the feasible live LAB counts and the declaration of the manufacturing companies. The recovered viable bacteria of pharmaceutical probiotic preparations ranged between (6.2 -7.3) × 1010 at 37 °C and (5.33-7.1) × 1010 at 25 °C, the claimed (9-10) × 1010 colony forming unit (CFU)/g. The encapsulated Lactobacillus acidophilus (LAB 1), L. bulgaricus (LAB 2), Lactococcus lactis (LAB 3) and Bifidobacterium bifidum (LAB 4) in OJ was resistant to drop out their viability as quickly as the free-form probiotic bacteria and >106 CFU/mL were still appeared after 6 wks of storage. Unencapsulated probiotics was found to have a significant reduction in viability in OJ at both 37 °C and 4 °C temperatures. However, the microencapsulation process significantly reduced the loss of viability of four probiotic bacteria as well as the control of acidification of OJ at 4 °C. CONCLUSIONS: The loss of potency and spoiled food associated with pathogenic microbial growth are serious problems in tropical countries including Bangladesh. The biopreserved OJ will become an important functional food due to its expansion of shelf-time, market reputation, profits and innate tastes. This report has an indication that the combination of these four LAB may become good candidate for the development of an OJ with functional characteristics

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

Abstract 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

Investigation on Antioxidant Activities of Six Indigenous Plants of Bangladesh

Abstract: In the present study, the antioxidant potential of methanolic extracts of the leaves of Aegle marmelos Corr.(Local Name-Bel), Abroma augusta Linn (Local Name-Ulot Kambal), Lagerstroemia speciosa (Local Name-Jarul), Cassia fistula (Local Name-Bador Lathi), Anthocephalus chinensis (Local Name-Kadam), Syzygium cumini Skeel (Local Name-Jam), was evaluated. The extracts were investigated for its antioxidant activity using hydrogen donation assay method. The extracts showed significant antioxidant activities in hydrogen donation assay compared to the standard antioxidant (Ascorbic Acid) in a dose dependent manner. All the extracts showed potent antioxidant activity, of which the methanolic 50 extract of Abroma augusta Linn. demonstrated the strongest antioxidant activity with the IC value of 51.9786mg ml . The other extracts of plants also showed significant antioxidant activity. -

Flavonoids isolated from Tridax procumbens (TPF) inhibit osteoclasts differentiation and bone resorption

BACKGROUND: The Tridax procumbens flavonoids (TPF), are well known for their medicinal properties among local natives. The TPF are traditionally used for dropsy, anaemia, arthritis, gout, asthma, ulcer, piles, and urinary problems. It also used in treating gastric problems, body pain, and rheumatic pains of joints. The TPF have been reported to increase osteogenic functioning in mesenchymal stem cells. However, their effects on osteoclastogenesis remain unclear. The TPF isolated from T. procumbens and investigated the effects of the TPF inhibit on osteoclast differentiation and bone resorption activities using primary osteoclastic cells. Osteoclast formation was assessed by counting the number of tartrate resistant acid phosphatase (TRAP) positive multinucleated cells and by measuring both TRAP activities. RESULTS: The TPF significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in primary osteoclastic cells. The TPF also decreased the expression of mRNAs related to osteoclast differentiation, including Trap, Cathepsin K, Mmp-9, and Mmp-13 in primary osteoclastic cells. The treatment of primary osteoclastic cells with the TPF decreased Cathepsin K, Mmp-9, and Mmp-13 proteins expression in primary osteoclastic cells. CONCLUSION: These results indicated that TPF inhibit osteoclastogenesis and pits formation activities. Our results suggest that the TPF could be a potential anti-bone resorptic 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 osteoporosi

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