Decoding the Mechanism of Shen Qi Sha Bai Decoction in Treating Acute Myeloid Leukemia Based on Network Pharmacology and Molecular Docking

Traditional Chinese Medicine (TCM) has been shown to be efficacious in treating leukemia for thousands of years. It has been shown that Shen Qi Sha Bai Decoction (SQSBD) has been extensively used in the treatment of acute myeloid leukemia (AML). However, the mechanism of SQSBD in treating AML remains unclear. In this study, we employed network pharmacology to analyze the potential active components and elucidate molecular mechanism of SQSBD in treating AML. A total of 268 active components were identified from SQSBD, among which 9 key components (Quercetin, luteolin, kaempferol, licochalcone A, formononetin, wogonin, β-sitosterol, oroxylin A, naringenin, and baicalein) were hit by the 6 hub targets (CDK1, MAPK1, JUN, PCNA, HSB1, STAT3) associated with leukemia. Molecular docking showed that two core active components, quercetin and licochalcone A, exhibited the highest component-like properties (DL), and could bind well to CDK1 and MAPK1 protein. The experimental validation of these two components showed that quercetin inhibited cell growth through CDK1 dephosphorylation-mediated cell cycle arrest at G2/M phase in human AML U937 and HL60 cells, and licochalcone A induced cell differentiation in these leukemia cells via activation of MAPK1 and upregulation of CD11b. All these results indicate that SQSBD is effective in the treatment of AML, and quercetin and licochalcone A are the major candidate compounds for AML treatment.

Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

Hepatocellular carcinoma is a malignancy with a low survival rate globally, and there is imperative to unearth novel natural phytochemicals as effective therapeutic strategies. Licochalcone A is a chalcone from Glycyrrhiza that displayed various pharmacological efficacy. A globally transcriptome analysis was carried out to reveal the gene expression profiling to explore Licochalcone A's function as an anti-cancer phytochemical on HepG2 cells and investigate its potential mechanisms. Altogether, 6,061 dysregulated genes were detected (3,414 up-regulated and 2,647 down-regulated). SP1 was expected as the transcription factor that regulates the functions of most screened genes. GO and KEGG analysis was conducted, and the MAPK signaling pathway and the FoxO signaling pathway were two critical signal pathways. Protein-protein interaction (PPI) network analysis based on STRING platform to discover the hub genes (MAPK1, ATF4, BDNF, CASP3, etc.) in the MAPK signaling pathway and (AKT3, GADD45A, IL6, CDK2, CDKN1A, etc.) the FoxO signaling pathway. The protein level of essential genes that participated in significant pathways was consistent with the transcriptome data. This study will provide an inclusive understanding of the potential anti-cancer mechanism of Licochalcone A on hepatocellular, signifying Licochalcone A as a promising candidate for cancer therapy.

Pengembangan dan Optimasi Kapsul Mikrosfer Ekstrak Licorice sebagai Bentuk Sediaan Oral Extended Release Kanker Payudara

Kanker payudara adalah kanker dengan angka kejadian tertinggi pada wanita. Protein yang terlibat dalam proses metastasis pada kanker adalah high mobility group box 1 (HMGB1). Licorice (Glycyrrhiza glabra) dilaporkan memiliki efek farmakologi antikanker dan ekstrak etanol roasted licorice dapat mengurangi viabilitas metastasis sel kanker. Sistem penghantaran mikrosfer merupakan serbuk padat terdiri dari polimer, crosslinked, dan bahan aktif yang dapat memberikan efek terapeutik diperpanjang. Penelitian ini bertujuan untuk memprediksi kemampuan licorice menghambat protein HMGB1 melalui molecular docking study dan mengetahui konsentrasi crosslinked natrium tripolifosfat yang paling optimal dalam formula kapsul mikrosfer ekstrak licorice. Metode penelitian dilakukan dengan uji in silico berupa molecular docking dan uji ADMET, formulasi kapsul mikrosfer ekstrak licorice dengan variasi konsentrasi natrium tripolifosfat 3%, 6%, dan 9%, dan uji evaluasi mutu sediaan meliputi morfologi dan ukuran, sifat alir, penetapan kandungan, organoleptik, kadar air, waktu hancur, dan keseragaman bobot. Data hasil uji evaluasi dianalisis secara statistik menggunakan uji Kruskal Wallis melalui IBM SPSS 28.0. Hasil yang diperoleh yakni senyawa glycyrrhetic acid, liquiritin apioside, dan liquiritin berpotensi menghambat protein HMGB1, glycyrrhetic acid dan licochalcone A merupakan substrat CYP450 3A4, dan delapan senyawa merupakan substrat P-gp dengan kelas toksisitas rendah. Kemudian tidak ada perbedaan yang signifikan pada hasil uji ketiga formula namun konsentrasi crosslinked natrium tripolifosfat yang paling optimum dapat terlihat melalui uji evaluasi mutu sediaan. Kesimpulan penelitian ini adalah senyawa glycyrrhetic acid, liquiritin apioside, dan liquiritin dalam licorice berpotensi menghambat HMGB1 dan formula mikrosfer yang memenuhi uji evaluasi paling baik adalah formula dengan konsentrasi natrium tripolifosfat 3%.

The flavonoid Licochalcone A induces tegumental damages in Schistosoma mansoni and impairs its oviposition in vitro

In this study, Licochalcone A (LicoA) was investigated in in vitro and in vivo assays. The survival of worms in culture, the pattern of oviposition, the count of intact tubers and the integrity of the coat were adopted in the in vitro tests. After the animals were perfused, the number of worms recovered, their location and the oogram study were the parameters analyzed to signal the existence of potential schistosomicidal activity in vivo. We observed reduction on the survival, integument integrity and reproduction of adult worms in vitro. Murine models did not show a significant difference in the parasitological parameters analyzed that indicate activity against the worms with an oral single dose of 25 mg/ kg of LicoA or two intraperitoneal injection of 50 mg/ kg LicoA. Nevertheless, it is too early to completely exclude the schistosomicide activity of LicoA, considering that the used dosage form could not provide a regular absorption of the drug.