Hepatoprotective Activity of Pirdot Leaves (Saurauia vulcani Korth) Ethanol Extract in Laboratory Rats (Rattus norvegicus) and Characterization of Bioactive Compounds Using a Molecular Docking Approach

AIM: The hepatoprotective activities of bioactive compounds Pirdot were investigated in vivo and in silico. METHODS: In this study, the completely randomized design non-factorial was experimentally to assess the value of SGPT and SGOT and twenty four adult male rats were divided into four groups : group G0, control group; group G1, a treated group received 0.1 ml sheep red blood cell; group G2, a treated group received 500 mg ethanol extract Pirdot; group G3, a group treated received 500 mg ethanol extract Pirdot and 0,1 ml sheep red blood cell. On thirty one days of treatment, the blood of all rats group were taken to value SGPT and SGOT using DiaLab kit. Furthermore, the molecular docking study was done to analyse molecular interaction that COX-2 and TNF-α were the primary target protein of bioactive compounds of Pirdot associated with hepatoprotective activities. In addition, it tends to be the target of non-steroidal anti-inflammatory drugs such as Ibuprofen. RESULTS: The results show SGOT and SGPT value significantly [p<0.05] decreased on Group G2 and G3. Moreover, the bioactive compounds of Pirdot, such as Pomolic acid and Ursolic acid tend to be the potential compound on liver protection. Moreover, Pomolic acid has a good binding affinity -14.6 kcal mol-1 with COX-2 Protein and the binding affinity of cis-3-O-p-hydroxycinnamoyl Ursolic acid was -15.1 kcal mol-1 associated with TNF-α Protein. CONLUSION: Pirdot Leaves (Saurauia vulcani Korth.) Ethanol Extract showed Hepatoprotective activity in rats (Rattus norvegicus). Molecular docking approach showed that pomolic acid has a good binding affinity with COX-2 Protein and TNF-α Protein.

Natural Compounds as Potential Regulators of the Phosphatidylinositol 3′ Kinase (PI3K) Pathway in Breast Cancer

Breast cancer is one of the most prevalent forms of cancer in women both globally and in India. Although breast cancer is characterized by different molecular subtypes, a majority of breast cancers appear to have mutations in the phosphatidylinositol 3′ kinase (PI3K)/ protein kinase B (Akt) pathway. Dysregulation of the PI3K/ Akt pathway in breast cancers plays important roles in promoting tumour growth, proliferation and invasion. Targeting PI3K mediated signalling cascades could be therefore of value for breast cancer treatment. Studies with synthetic inhibitors of the PI3K/ Akt pathway have yielded positive results but the efficacy shown by many of these inhibitors appear to be compromised by deleterious side effects. An alternative to syn-thetic inhibitors is the use of natural phytochemical compounds with anti-tumorigenic potential like apigenin, pomolic acid, resveratrol and its deriva-tives, curcumin, epigallocatechin-3 gallate and thymoquinone as potential inhibitors of PI3K/Akt signalling in breast cancer and such a strategy could lead to lesser side effects and a lower treatment cost. The current study ex-amines the importance of the PI3K pathway in breast cancer and discusses how regulation of aberrant signalling through this pathway by natural com-pounds could play an important role in breast cancer therapy.

Effectiveness of Bioactive Compound as Antibacterial and Anti-Quorum Sensing Agent from Myrmecodia pendans: An In Silico Study

Background: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that Myrmecodia pendans (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. This study aims to investigate and predict the action mode of antibacterial compounds with specific proteins by following the molecular docking approach. Methods: butein (1), biflavonoid (2), 3″-methoxyepicatechin-3-O-epicatechin (3), 2-dodecyl-4-hydroxylbenzaldehyde (4), 2-dodecyl-4-hydroxylbenzaldehyde (5), pomolic acid (6), betulin (7), and sitosterol-(6′-O-tridecanoil)-3-O-β-D-glucopyranoside (8) from M. pendans act as the ligand. Antibiotics or substrates in each protein were used as a positive control. To screen the bioactivity of compounds, ligands were analyzed by Prediction of Activity Spectra for Substances (PASS) program. They were docked with 12 proteins by AutoDock Vina in the PyRx 0.8 software application. Those proteins are penicillin-binding protein (PBP), MurB, Sortase A (SrtA), deoxyribonucleic acid (DNA) gyrase, ribonucleic acid (RNA) polymerase, ribosomal protein, Cytolysin M (ClyM), FsrB, gelatinase binding-activating pheromone (GBAP), and PgrX retrieved from UniProt. The docking results were analyzed by the ProteinsPlus and Discovery Studio software applications. Results: most compounds have Pa value over 0.5 against proteins in the cell wall. In nearly all proteins, biflavonoid (2) has the strongest binding affinity. However, compound 2 binds only three residues, so that 2 is the non-competitive inhibitor. Conclusion: compound 2 can be a lead compound for an antibacterial agent in each pathway.

Repurposing Multi-Targeting Plant Natural Product Scaffolds In Silico Against SARS-CoV-2 Non-Structural Proteins Implicated in Viral Pathogenesis

<p>Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. Thus, this study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting <i>in silico</i> key sites in the structures of SARS-CoV-2 nsps. Moreover, structures of the anti-HIV compounds were considered for druggability and toxicity. 104 anti-HIV phytochemicals were subjected to molecular docking with papain-like protease (nsp3), 3-chymotrypsin-like protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), SAM-dependent 2’-<i>O-</i>methyltransferase (nsp16) and its cofactor (nsp10), and endoribonuclease (nsp15). Drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top ten compounds per nsp were predicted using SwissADME. Their toxicity was also determined using OSIRIS Property Explorer.</p> <p>Results: Among the twenty-seven top-scoring compounds, the polyphenolic natural products amentoflavone (<b>1</b>), robustaflavone (<b>4</b>), punicalin (<b>9</b>), volkensiflavone (<b>11</b>), rhusflavanone (<b>13</b>), morelloflavone (<b>14</b>), hinokiflavone (<b>15</b>), and michellamine B (<b>19</b>) were multi-targeting and had the strongest affinities to at least two of the nsps (Binding Energy = -7.7 to -10.8 kcal/mol). Friedelin (<b>2</b>), pomolic acid (<b>5</b>), ursolic acid (<b>10</b>), garcisaterpenes A (<b>12</b>), hinokiflavone (<b>15</b>), and digitoxigenin-3-<i>O-</i>glucoside (<b>17</b>) were computationally druggable. Moreover, compounds <b>5</b> and <b>17</b> showed good gastrointestinal absorptive property. Most of the compounds were also predicted to be non-toxic.</p> <p>Conclusions: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 nsp3, 5, 10, 12, 13, 15, and 16, and can therefore be used as prototypes for anti-COVID-19 drug design.</p>

Repurposing Multi-Targeting Plant Natural Product Scaffolds In Silico Against SARS-CoV-2 Non-Structural Proteins Implicated in Viral Pathogenesis

<p>Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. Thus, this study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting <i>in silico</i> key sites in the structures of SARS-CoV-2 nsps. Moreover, structures of the anti-HIV compounds were considered for druggability and toxicity. 104 anti-HIV phytochemicals were subjected to molecular docking with papain-like protease (nsp3), 3-chymotrypsin-like protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), SAM-dependent 2’-<i>O-</i>methyltransferase (nsp16) and its cofactor (nsp10), and endoribonuclease (nsp15). Drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top ten compounds per nsp were predicted using SwissADME. Their toxicity was also determined using OSIRIS Property Explorer.</p> <p>Results: Among the twenty-seven top-scoring compounds, the polyphenolic natural products amentoflavone (<b>1</b>), robustaflavone (<b>4</b>), punicalin (<b>9</b>), volkensiflavone (<b>11</b>), rhusflavanone (<b>13</b>), morelloflavone (<b>14</b>), hinokiflavone (<b>15</b>), and michellamine B (<b>19</b>) were multi-targeting and had the strongest affinities to at least two of the nsps (Binding Energy = -7.7 to -10.8 kcal/mol). Friedelin (<b>2</b>), pomolic acid (<b>5</b>), ursolic acid (<b>10</b>), garcisaterpenes A (<b>12</b>), hinokiflavone (<b>15</b>), and digitoxigenin-3-<i>O-</i>glucoside (<b>17</b>) were computationally druggable. Moreover, compounds <b>5</b> and <b>17</b> showed good gastrointestinal absorptive property. Most of the compounds were also predicted to be non-toxic.</p> <p>Conclusions: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 nsp3, 5, 10, 12, 13, 15, and 16, and can therefore be used as prototypes for anti-COVID-19 drug design.</p>

Pomolic acid in persimmon peel suppresses the increase in glycerol-3 phosphate dehydrogenase activity in 3T3-L1 adipocytes

ABSTRACT Persimmon peels, though usually discarded, are useful sources of nutraceuticals. In this study, persimmon peel–derived pomolic acid was found to suppress the increase in the activity of glycerol-3 phosphate dehydrogenase, a neutral fat synthesis-related enzyme, in 3T3-L1 adipocytes, whereas oleanolic and ursolic acids did not exert this effect. Therefore, persimmon peel may be an effective functional food material.

Comparative Phytochemical Screening and Cytotoxic Efficacy of Endemic Cephalaria tuteliana

Phytochemical investigation of Cephalaria tuteliana (Caprifoliaceae) endemic to Turkey was carried out for the first time. Thirteen compounds were isolated, including 2 triterpenoid sapogenins, 10 saponins, and 1 iridoid glycoside. This is the first report of the isolation of pomolic acid, tormentic acid, and 3- O-α-l-rhamnopyranosyl-(1→3)- β-d-glucopyranosyl hederagenin, not only from the Cephalaria genus, but also from the Caprifoliaceae family. The structures of the isolated compounds were elucidated by a combination of spectroscopy, including one- and two-dimensional nuclear magnetic resonance, and by comparison with the reported data in the literature. Two triterpene sapogenins, hederagenin and oleanoic acid, the latter being the most typical sapogenin of the oleanane type of triterpene saponins, were evaluated by the MTT method for their cytotoxic effect against A549, HeLa, PANC1, and SHSY5Y cancer cells, and the noncancerous HEK293 cell line. The cytotoxic activity of triterpene aglycones was discussed in detail and a structure-activity relationship was established. C. tuteliana may be considered as a useful source for developing new cytotoxic and immunotherapeutic agents due to its biologically active saponin content.