Kobophenol A

Int Immunopharmacol. 2013 Nov;17(3):704-13.

Kobophenol A enhances proliferation of human osteoblast-like cells with activation of the p38 pathway.[Pubmed: 24021754]

Bone cell proliferation, bone formation, and bone resorption are the main factors involved in the homeostasis of the bone mass. Osteoblast death is a problem experienced by postmenopause women. Herbal medicines have attracted considerable attention for use as a drug or a drug substitute in the treatment of bone-related diseases, such as osteoporosis.
METHODS AND RESULTS:
This study investigated the effects of Kobophenol A on the proliferation in human osteoblast cells. Kobophenol A stimulated the proliferation of osteoblast cells by the increases in DNA synthesis and the enhancement of cell cycle progression. Kobophenol A stimulation induced the expression of the cyclin B1 and cyclin-dependent kinase 1 (CDK1). Treatment of osteoblast cells with p38 MAPK inhibitor SB203580 significantly inhibited Kobophenol A-enhanced proliferation. In addition, Kobophenol A induced phosphorylation of p38 MAPK. Treatment of osteoblast cells with Kobophenol A resulted in improvement of ROS scavenging activity. Moreover, Kobophenol A treatment up-regulated the Bcl-2 level, but down-regulated the level of Bax expression. We also demonstrate that Kobophenol A increased alkaline phosphatase (ALP) activity after 2 days.
CONCLUSIONS:
Taken together, the results of this study reveal that Kobophenol A has proliferative effects and enhances ALP activity in osteoblast cells and these findings provide insights into the development of a therapeutic approach of Kobophenol A in the prevention of osteoporosis and other bone disorders.

Chem Pharm Bull (Tokyo). 2014;62(7):713-8. Epub 2014 Apr 24.

Kobophenol A inhibits sodium nitroprusside-induced cardiac H9c2 cell death through suppressing activation of JNK and preserving mitochondrial anti-apoptotic Bcl-2 and Mcl-1.[Pubmed: 24759620]

Sodium nitroprusside (SNP) releases nitric oxide (NO), a powerful vasodilator, and thus widely used in intensive care unit for treating hypertension emergency. However, cardiac toxicity after SNP administration is a clinical problem.
METHODS AND RESULTS:
For finding a natural compound that suppressing SNP-induced cardiac toxicity, we tested the protective potential of Kobophenol A (Kob A), purified from the root of Caragana sinica, against the toxic effects of SNP. The severe cardiac H9c2 cell death was induced by SNP (2 mM) treatment. Kob A ameliorated SNP-induced cardiac H9c2 cell death, and this protective effect of Kob A may be related to the inhibition of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase activation following SNP administration. In addition, the downregulation of cellular Bcl-2 and Mcl-1 levels by SNP exposure was strongly abrogated in the presence of Kob A.
CONCLUSIONS:
These biological properties of Kob A might provide insights into developing new cardioprotectant against SNP-induced cardiac cell death.

J. Phys. Chem. Lett. 2021, 12, 7, 1793–1802

Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19[Pubmed: 33577324]

In the search for inhibitors of COVID-19, we have targeted the interaction between the human angiotensin-converting enzyme 2 (ACE2) receptor and the spike receptor binding domain (S1-RBD) of SARS-CoV-2. Virtual screening of a library of natural compounds identified Kobophenol A as a potential inhibitor. Kobophenol A was then found to block the interaction between the ACE2 receptor and S1-RBD in vitro with an IC50 of 1.81 ± 0.04 μM and inhibit SARS-CoV-2 viral infection in cells with an EC50 of 71.6 μM. Blind docking calculations identified two potential binding sites, and molecular dynamics simulations predicted binding free energies of −19.0 ± 4.3 and −24.9 ± 6.9 kcal/mol for Kobophenol A to the spike/ACE2 interface and the ACE2 hydrophobic pocket, respectively. In summary, Kobophenol A, identified through docking studies, is the first compound that inhibits SARS-CoV-2 binding to cells through blocking S1-RBD to the host ACE2 receptor and thus may serve as a good lead compound against COVID-19.

Bioorg Med Chem Lett. 2007 Apr 1;17(7):1879-82. Epub 2007 Jan 27.

Neuroprotective effects of kobophenol A against the withdrawal of tropic support, nitrosative stress, and mitochondrial damage in SH-SY5Y neuroblastoma cells.[Pubmed: 17300930]

This study examined the neuroprotective effects of Kobophenol A (kob A), oligomeric stillbene, and a resveratrol tetramer. Neuronal death induced by the withdrawal of tropic support was ameliorated by Kobophenol A. The protective effect of Kobophenol A against nitrosative/oxidative or mitochondrial damages resulted in the inhibition of the ROS, intracellular calcium ion level, and mitochondrial transmembrane potential changes on SH-SY5Y cells.

Int Immunopharmacol. 2011 Sep;11(9):1251-9.

Protective effect of kobophenol A on nitric oxide-induced cell apoptosis in human osteoblast-like MG-63 cells: involvement of JNK, NF-κB and AP-1 pathways.[Pubmed: 21511059]

Nitric oxide (NO) is a multifunctional signaling molecule and the cytotoxic species responsible for a variety of pathologic disorders including bone destruction. High NO levels induce the apoptosis of osteoblasts and decrease the bone mineral density.
METHODS AND RESULTS:
We investigated the influence of Kobophenol A (kob A) on apoptosis in cultured human osteoblast-like MG-63 cells. Direct NO donor sodium nitroprusside (SNP) that has been recognized as an inducer of apoptosis in various cell lines significantly induced cell death and NO production in MG-63 cells. Coincubation of kob A in SNP-treated MG-63 cells resulted in a significant protection against NO-induced cell death. This is associated with increase in intracellular reactive oxygen species (ROS) scavenging activity and the inhibition of decrease in mitochondrial membrane potential (MMP) by kob A. We also found that kob A inhibited the down-regulation of Bcl-2 and Bcl-X(L), whereas the level of Bax expression was decreased by kob A treatment in SNP-treated MG-63 cells. Furthermore, kob A inhibited SNP-induced phosphorylation of JNK and c-Jun, and SNP-induced reduction in NF-κΒ and AP-1 activities, implicating that protective effect of kob A may occur through the regulation of JNK, NF-κΒ and AP-1 signaling pathways.
CONCLUSIONS:
Together, these findings suggest that kob A has a protective effect against NO-mediated osteoblast apoptosis and might be a plausible candidate for treatment of inflammatory bone diseases relevant to osteoblast cell death.