NATURAL PRODUCTS AS AN IMPORTANT LEADS FOR DISCOVERY OF NEW ANTITUBERCULAR AGENTS: A REVIEW

There is a very much need for a discovery of new molecules a potent molecule that can cure tuberculosis and prevent the recurrence. A multidisciplinary approach is required to procure a potent bioactive compound and this includes expertise in the fields of ethnobotany, ethnopharmacology and Phytochemistry. The present communication acts as a bioprospecting source for the drug discovery against tuberculosis, including several anti tubercular agents which is used by used by tribal people and prescribed by THPS which showed a good inhibition rate. Therefore, this review strives to describe the literature on the traditional plants/potent molecules those have been proved to have antimicrobial activity and to provide essential discussion and accelerate the research.Â

Phytochemical evaluation and anti-psoriatic activity of the ethanolic extract of the leaves of Momordica charantia

Psoriasis is a chronic, inflammatory, multi factorial disease. Topical chemical agents are used to treat psoriasis, despite their lower effectiveness or ineffective effects. Herbal medicine can be one of the alternative treatment methods. Momordica charantia is traditionally used to treat skin diseases, especially psoriasis. The main phytochemicals responsible for antipsoriatic activity is stigmasterol, taraxerol, lofenol, phenylpropanoids and squalene. The alcoholic soxhlation method was used to obtain the percentage phytochemical yield of 13.36% w/w, which was used for antipsoriatic activity using a mouse tail model of psoriasis. The extract produced significant differentiation of the epidermis as evidenced by the degree of orthokeratosis 70.18 ± 2.64% compared to the negative control 17.30 ± 4.09%. This was equivalent to the effect of the standard positive control, tazarotene gel (0.1%), which showed a degree of orthokeratosis of 90.03 ± 2.00%. The extract showed an overall antipsoriatic activity of 63.94%

Phytochemical evaluation and anti-psoriatic activity of the ethanolic extract of the leaves of Thespesia populnea

Psoriasis is a chronic, mild and common inflammatory skin condition. Still an ideal treatment for psoriasis, effective, safe, convenient, and economical is not available. In this scenario, the search for suitable alternative treatments with minimal side effects is necessary. Plants can be effective and alternative in this regard. Therefore, this article discusses the leaves of the plants Thespesia populnea (Malvaceae) that are traditionally used in the treatment of psoriasis. The present study aimed to assess anti-psoriatic activity. The dried leaves of the plants were subjected to soxhlation with 95% ethanol and phytochemical studies were performed. The anti-psoriatic activity was evaluated by the Mouse-Tail model. It is a relatively sensitive and reproducible morphometric method that allows quantitative evaluation of the effects of anti-psoriatics through epidermal differentiation. Extracts were applied topically at a dose of 500mg/kg over 14 days and at the end, the animals were sacrificed, longitudinal histological sections were made of the tail skin and the degree of orthokeratosis was determined. It was significantly (P <0.05) increased by the ethanolic extract of Thespesia populnea (52.86±2.86) compared to the control (17.30±4.09). In relative epidermal thickness, the ethanolic extract of Thespesia populnea (92.68±8.8) showed a significant difference (P <0.05) compared to the control (100±10.7). The data obtained suggest that the selected plant has anti-psoriatic activity and confirms its traditional use in the treatment of psoriasis

ANTIOXIDANT AND ANTI-PROLIFERATIVE EFFECTS OF AN ETHYL ACETATE FRACTION OF THE HYDRO-ETHANOLIC EXTRACT OF SYNEDRELLA NODIFLORA (L) GAERTN

Objective: Synedrella nodiflora is traditionally used in the treatment of several ailments. Pharmacologically, this plant has anticonvulsant, sedative, anti-nociceptive and anti-proliferative effects. This study further investigated S. nodiflora for its antioxidant and in vitro inhibition of cancerous cell lines. Methods: Phytochemical assays, and the DPPH radical scavenging method were employed in preliminary screening for antioxidant activities of the crude hydro-ethanolic extract (SNE) and resulting fractions. The potent ethyl acetate fraction (EAF), was further investigated for total phenol and flavonoid contents, reducing power, lipid peroxidation potential, and cytotoxic effects on human breast cancer (MCF-7), leukemic (Jurkat), and normal liver (Chang’s liver) cell lines. Results: The extract contained phenols, flavonoids, tannins, glycosides, sterols, terpenoids, and alkaloids. It scavenged for DPPH with an IC50 of 114 µg/ml, whereas that of EAF was 8.9 µg/ml. EAF prevented peroxidation of egg lecithin at an IC50 of 24.01±0.08 µg/ml. These IC50s are four and three times lower than the reference standards. EAF produced anti-proliferative effects against MCF-7, and Jurkat cell lines with IC50s of 205.2 and 170.9 µg/ml, respectively. EAF had a high IC50 of 252.2 µg/ml against Chang’s liver cells. At 0.1 mg/ml EAF had similar total flavonoid content to SNE, but a significantly higher total phenol content. Conclusion: The ethyl acetate fraction of S. nodiflora, exhibited the most potent antioxidant activity. It inhibited the proliferation of breast and leukemic cancer cell lines, whiles having weak cytotoxic effect on normal liver cells. These can be explored for further drug development

The Endosomal Escape Vehicle Platform Enhances Delivery of Oligonucleotides in Preclinical Models of Neuromuscular Disorders

Biological therapeutic agents are highly targeted and potent but limited in their ability to reach intracellular targets. These limitations often necessitate high therapeutic doses and can be associated with less-than-optimal therapeutic activity. One promising solution for therapeutic agent delivery is use of cell-penetrating peptides. Canonical cell-penetrating peptides, however, are limited by low efficiencies of cellular uptake and endosomal escape, minimal proteolytic stability, and toxicity. To overcome these limitations, we designed a family of proprietary cyclic cell-penetrating peptides that form the core of our endosomal escape vehicle technology capable of delivering therapeutic agent-conjugated cargo intracellularly. We demonstrated the therapeutic potential of this endosomal escape vehicle platform in preclinical models of muscular dystrophy with distinct disease etiology. An endosomal escape vehicle-conjugated, splice-modulating oligonucleotide restored dystrophin protein expression in striated muscles in the mdx mouse, a model for Duchenne muscular dystrophy. Furthermore, another endosomal escape vehicle-conjugated, sterically blocking oligonucleotide led to knockdown of aberrant transcript expression levels in facioscapulohumeral muscular dystrophy patient-derived skeletal muscle cells. These findings suggest a significant therapeutic potential of our endosomal escape vehicle conjugated oligonucleotides for targeted upregulation and downregulation of gene expression in neuromuscular diseases, with possible broader application of this platform for delivery of intracellular biological agents

Intrusion detection and classification with autoencoded deep neural network

A Network Intrusion Detection System is a critical component of every internet connected system due to likely attacks from both external and internal sources. A NIDS is used to detect network born attacks such as denial of service attacks, malware, and intruders that are operating within the system. Neural networks have become an increasingly popular solution for network intrusion detection. Their capability of learning complex patterns and behaviors make them a suitable solution for differentiating between normal traffic and network attacks. In this paper, we have applied a deep autoencoded dense neural network algorithm for detecting intrusion or attacks in network connection and evaluated the algorithm with the benchmark NSL-KDD dataset. Our results showed an excellent performance with an overall detection accuracy of 99.3% for Probe, Remote to Local, Denial of Service and User to Root type of attacks. We also presented a comparison with recent approaches used in literature which showed a substantial improvement in terms of accuracy and speed of detection with the proposed algorithm

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Endostatin expression in pancreatic tissue is modulated by elastase

Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, we found mature 20 kDa endostatin in cancer tissue but not in normal tissue. Several endostatin-related peptides of higher mol wt were present in both tissues. Extracts from normal tissue were able to degrade exogenous endostatin, whereas extracts from cancer were without effect. Although the exocrine pancreas secretes inactive proenzymes of trypsin, chymotrypsin and elastase, their possible role in this degradation was examined. The trypsin/chymotrypsin inhibitor, Glycine max, did not prevent the degradation of endostatin by normal pancreatic extracts but elastatinal, a specific inhibitor of elastase, reduced the rate of degradation. Extracts of pancreatic tumours did not express any detectable elastase activity, but an elastase (Km 1.1 mM) was expressed by extracts of normal pancreas. We conclude that endostatin is present and stable in pancreatic cancer tissues, which may explain their avascular nature, but that normal pancreatic tissue expresses enzymes, including elastase, which rapidly degrade endostatin. The stability of endostatin may have implications for its therapeutic use

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy