Modeling of Human Prokineticin Receptors: Interactions with Novel Small-Molecule Binders and Potential Off-Target Drugs

The Prokineticin receptor (PKR) 1 and 2 subtypes are novel members of family A GPCRs, which exhibit an unusually high degree of sequence similarity. Prokineticins (PKs), their cognate ligands, are small secreted proteins of ∼80 amino acids; however, non-peptidic low-molecular weight antagonists have also been identified. PKs and their receptors play important roles under various physiological conditions such as maintaining circadian rhythm and pain perception, as well as regulating angiogenesis and modulating immunity. Identifying binding sites for known antagonists and for additional potential binders will facilitate studying and regulating these novel receptors. Blocking PKRs may serve as a therapeutic tool for various diseases, including acute pain, inflammation and cancer.Ligand-based pharmacophore models were derived from known antagonists, and virtual screening performed on the DrugBank dataset identified potential human PKR (hPKR) ligands with novel scaffolds. Interestingly, these included several HIV protease inhibitors for which endothelial cell dysfunction is a documented side effect. Our results suggest that the side effects might be due to inhibition of the PKR signaling pathway. Docking of known binders to a 3D homology model of hPKR1 is in agreement with the well-established canonical TM-bundle binding site of family A GPCRs. Furthermore, the docking results highlight residues that may form specific contacts with the ligands. These contacts provide structural explanation for the importance of several chemical features that were obtained from the structure-activity analysis of known binders. With the exception of a single loop residue that might be perused in the future for obtaining subtype-specific regulation, the results suggest an identical TM-bundle binding site for hPKR1 and hPKR2. In addition, analysis of the intracellular regions highlights variable regions that may provide subtype specificity

Standarisasi simplisia kering daun beluntas (Pluchea indica L.) dari tiga daerah berbeda

Beluntas (Pluchea indica L.) biasa digunakan sebagai tanaman pagar dan secara tradisional daunnya digunakan sebagai lalapan atau obat untuk menghilangkan bau badan, obat penurun panas, obat batuk, dan obat antidiare. Seiring dengan meningkatnya teknologi bahan alam dan kecenderungan masyarakat dalam penggunaan produk yang berasal dari bahan alam terutama tumbuhan obat. Maka, diperlukan adanya suatu acuan yang memuat persyaratan mutu bahan alam yang sesuai digunakan sebagai bahan obat. Penelitian ini bertujuan untuk menetapkan profil standarisasi spesifik dan non spesifik dari simplisia kering daun beluntas. Standarisasi daun beluntas yang meliputi parameter spesifik dan parameter non spesifik, karakterisasi terhadap ciri-ciri mikroskopik daun beluntas (Pluchea indica L.), karakterisasi kandungan senyawa metabolit sekunder menggunakan kromatografi lapis tipis (KLT), Penetapan profil spektrum dengan menggunakan spektrofotometer Infrared (IR), dan penetapan kadar senyawa metabolit sekunder dengan spektrofotometri. Data yang diperoleh merupakan data deskriptif yang mencerminkan perolehan data dari 3 lokasi yang berbeda. Didapatkan hasil pengamatan mikroskopik simplisia daun beluntas mempunyai berkas pembuluh dengan penebalan spiral, stomata tipe anomositik, rambut penutup. persentase kadar sari larut etanol ≥5%, kadar sari larut air ≥26%, Hasil pengamatan skrining fitokimia hasil positif pada pengamatan alkaloid, flavonoid, fenol, steroid dan terpen. Kadar abu total <16%, kadar abu larut air <10%, kadar abu tidak larut asam <8%, susut pengeringan <12%, persen bahan asing <4%, pH 5

Standarisasi simplisia kering daun beluntas (Pluchea indica L.) dari tiga daerah berbeda

Beluntas (Pluchea indica L.) biasa digunakan sebagai tanaman pagar dan secara tradisional daunnya digunakan sebagai lalapan atau obat untuk menghilangkan bau badan, obat penurun panas, obat batuk, dan obat antidiare. Seiring dengan meningkatnya teknologi bahan alam dan kecenderungan masyarakat dalam penggunaan produk yang berasal dari bahan alam terutama tumbuhan obat. Maka, diperlukan adanya suatu acuan yang memuat persyaratan mutu bahan alam yang sesuai digunakan sebagai bahan obat. Penelitian ini bertujuan untuk menetapkan profil standarisasi spesifik dan non spesifik dari simplisia kering daun beluntas. Standarisasi daun beluntas yang meliputi parameter spesifik dan parameter non spesifik, karakterisasi terhadap ciri-ciri mikroskopik daun beluntas (Pluchea indica L.), karakterisasi kandungan senyawa metabolit sekunder menggunakan kromatografi lapis tipis (KLT), Penetapan profil spektrum dengan menggunakan spektrofotometer Infrared (IR), dan penetapan kadar senyawa metabolit sekunder dengan spektrofotometri. Data yang diperoleh merupakan data deskriptif yang mencerminkan perolehan data dari 3 lokasi yang berbeda. Didapatkan hasil pengamatan mikroskopik simplisia daun beluntas mempunyai berkas pembuluh dengan penebalan spiral, stomata tipe anomositik, rambut penutup. persentase kadar sari larut etanol ≥5%, kadar sari larut air ≥26%, Hasil pengamatan skrining fitokimia hasil positif pada pengamatan alkaloid, flavonoid, fenol, steroid dan terpen. Kadar abu total <16%, kadar abu larut air <10%, kadar abu tidak larut asam <8%, susut pengeringan <12%, persen bahan asing <4%, pH 5

Standarisasi Simplisia Kering Daun Beluntas (Pluchea indica L.) dari Tiga Daerah Berbeda

Indian Fleabane (Pluchea indica L.) are commonly used as hedgerows and traditionally the leaves are used as fresh salad or medicines to eliminate body odor, febrifuge, cough medicine, and antidiarrheal drugs. Along with the increasing technology of natural materials and the tendency of people to use products derived from natural materials, especially medicinal plants, a reference which contains the requirements for the quality of natural ingredients that are suitable for use as medicinal ingredients is needed. This research aims to determine the profile of specific and non specific standardization of dried powder of indian fleabane leaves. Standardization of indian fleabane leaves covers specific parameters and non specific parameters, characterization of microscopic characteristics of indian fleabane (Pluchea indica L.) leaves, characterization of the content of secondary metabolites using thin layer chromatography (TLC), determination of spectrum profiles using infrared spectrophotometer (IR), and determination of the levels of secondary metabolites by spectrofotometry. The data obtained is descriptive data that reflect the acquisition of data from 3 different locations. Based on microscopic observations indian fleabane leaf dried powder has vascular bundles with spiral thickening, anomocytic stomata, and multicellular trichomes. Ethanol solubility of dried powder indian fleabane is ≥5% while water solubility in water is ≥26%. The results of phytochemical screening showed positive results on the observations of alkaloids, flavonoids, phenols, steroids and terpenes. Total ash content i

Standarisasi Simplisia Kering Daun Beluntas (Pluchea Indica L.) dari Tiga Daerah Berbeda

Indian Fleabane (Pluchea indica L.) are commonly used as hedgerows and traditionally the leaves are used as fresh salad or medicines to eliminate body odor, febrifuge, cough medicine, and antidiarrheal drugs. Along with the increasing technology of natural materials and the tendency of people to use products derived from natural materials, especially medicinal plants, a reference which contains the requirements for the quality of natural ingredients that are suitable for use as medicinal ingredients is needed. This research aims to determine the profile of specific and non specific standardization of dried powder of Indian fleabane leaves. Standardization of Indian fleabane leaves covers specific parameters and non specific parameters, characterization of microscopic characteristics of Indian fleabane (Pluchea indica L.) leaves, characterization of the content of secondary metabolites using thin layer chromatography (TLC), determination of spectrum profiles using infrared spectrophotometer (IR), and determination of the levels of secondary metabolites by spectrofotometry. The data obtained is descriptive data that reflect the acquisition of data from 3 different locations. Based on microscopic observations Indian fleabane leaf dried powder has vascular bundles with spiral thickening, anomocytic stomata, and multicellular trichomes. Ethanol solubility of dried powder Indian fleabane is ≥5% while water solubility in water is ≥26%. The results of phytochemical screening showed positive results on the observations of alkaloids, flavonoids, phenols, steroids and terpenes. Total ash content i