Molecular insight of phytocompounds from Indian spices and its hyaluronic acid conjugates to block SARS-CoV-2 viral entry.

Human corona viral infection leads to acute breathing disease and death if not diagnosed and treated properly in time. The disease can be treated with the help of simple natural compounds, which we use in day-to-day life. These natural compounds act against several diseases but their drug targeting mechanism needs to be improved for more efficient and promising applications. In the present study five compounds (gingerol, thymol, thymohydroquinone, cyclocurcumin, hydrazinocurcumin) from three Indian medicinal plants (ginger, black cumin, turmeric) and its hyaluronic acid (HA) conjugates were docked against initially deposited spike structural proteins (PDB ID 6WPT) and its mutant variant D-614G (PDB ID 6XS6). Docking study result reveals that all the HA conjugates showed the most effective inhibitor of S-protein of initially deposited and D-614G variant forms of SARS-CoV-2. The compounds like Gingerol, Thymol, Thymohydroquinone, Cyclocurcumin, Hydrazinocurcumin, Hydroxychloroquinone, and hyaluronic acid conjugates inhibit the viral protein of both wild-type and mutated S-protein of SARS-CoV-2. The molecular docking studies of phytocompounds with initial deposited and variant spike protein targets show superior binding affinity than with the commercial repurposed viral entry inhibitor hydroxychloroquine. Further, the docking result was modeled using MD simulation study shows excellent simulation trajectories between spike proteins and HA conjugates spices constituents than its free form. DFT analysis was carried out to affirm the reason behind the highest binding affinity of HA conjugates over its free form towards SARS-CoV-2 spike protein targets. Further HA conjugates synthesis and its evaluation against SARS-CoV-2 in vitro studies are needed to prove our novel idea for an anti-viral drug.Communicated by Ramaswamy H. Sarma.

Syringic acid modulates molecular marker-involved cell proliferation, survival, apoptosis, inflammation, and angiogenesis in DMBA-induced oral squamous cell carcinoma in Syrian hamsters.

Despite, different medicinal phyto compounds giving an inexhaustible variety of anticancer drugs, potent signalling mechanism of leads  the key successes of anticancer agent, anti-inflammatory, induction of apoptosis, and antiangiogenic. The current study was conducted to estimate the effect of syringic acid (SA) on tumor necrosis factor-α (TNF-α)-mediated nuclear factor-κB (NF-κB) signaling pathways, inducing apoptosis and angiogenic signaling pathways in a hamster model by preneoplastic stages, histological, immunohistochemistry and immunoblots analysis. Hamsters were given oral cancer by painting 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) for 10 weeks. The DMBA-painted hamsters were treated with an effective dose (50 mg/kg body weight) of SA for 14 weeks. The results revealed that oral preadministration of SA to DMBA-treated hamster oral tumorigenesis significantly increased Bcl-2-associated X protein, caspases-3 and -9, and reduced B-cell lymphoma protein 2 and inflammatory cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, and TNF-α expression through NF-κB, and angiogenic vascular endothelial growth factor markers. Taken together, the current study suggests that SA prevents the DMBA-induced hamster buccal pouch carcinogenesis by triggering intrinsic apoptotic pathway via abrogation of the downstream signaling molecules such as COX-2, NF-κB, and TNF-α. This type of preventive strategy based on animal study will offer a means to design chemoprevention trials for humans.

JAK1/STAT3 regulatory effect of ß-caryophyllene on MG-63 osteosarcoma cells via ROS-induced apoptotic mitochondrial pathway by DNA fragmentation.

Currently, available treatment for osteosarcoma is combinational chemotherapy of doxorubicin, cisplatin, and methotrexate before and after surgery with overall 5-year survival rate of less than 40%. The present study was aimed to assess the anticancer effects of a phytochemical named ß-caryophyllene (BCP) in treating osteosarcoma. We assessed the effect of (BCP) on oxidative stress, proliferation, apoptosis, and inflammation in human bone cancer cells MG-63. Our results showed that BCP induced reactive oxygen species (ROS) generation at 20 µM concentration in MG-63 cells. The same dose was also shown to exhibit proapoptotic and antiproliferative effects in bone cancer cells MG-63. We demonstrated that the treatment of MG-63 cells with BCP prompted mitochondrial apoptosis via upregulation of Bax and caspase-3 and downregulation of Bcl-2 as well as prompted mitochondrial membrane potential. Our results also showed stimulation of Janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway in bone cancer MG-63 cells upon BCP treatment along with the induction of proinflammatory genes at the messenger RNA level. Overall results suggest that the treatment of MG-63 cells with BCP promotes apoptosis and inflammation via ROS and JAK1/STAT3 signaling pathway.

Syringic acid may attenuate the oral mucosal carcinogenesis via improving cell surface glycoconjugation and modifying cytokeratin expression.

Syringic acid (SRA) is an excellent anti-oxidant and anti-cancer property in various in vitro and in vivo studies. In the present study was modifying effect of SRA on 7,12-dimethylbenz(a)anthracene (DMBA) induced cell surface glycoconjugates (GCs) abnormalities in the plasma and buccal mucosa of golden Syrian hamster buccal pouch carcinogenesis (HBPCs). Topical application of DMBA three times a week for 10 weeks on the buccal pouches of the hamsters resulted in well developed squamous cell carcinoma. GCs status was assessed biochemically, histological and immunoexpression pattern of cytokeratin (CK) in the buccal mucosa of the DMBA treated hamsters. Elevated levels of GCs and CK expression were observed in DMBA alone treated hamsters. Oral pre-administration of SRA (50 mg/kg bw) positively modulates the GCs levels and CK expressions to near normal. The present findings suggested that SRA can protect cell surface GCs and CK expression during DMBA induced HBPCs.