Dataset Information

Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients.

ABSTRACT:

Background and aim

Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance.

Experimental procedure

hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups.

Results

Swertiamarin significantly (P < 0.05) reversed the expression of INSR-β, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17β-HSD and 3β-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17β-HSD and 3β-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes.

Conclusion

Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients.

SUBMITTER: Belani MA

PROVIDER: S-EPMC10024427 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients.

Belani Muskaan A MA Shah Preeti P Banker Manish M Gupta Sarita S SS

Journal of ovarian research 20230318 1

<h4>Background and aim</h4>Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance.<h4>Experimental procedure</h4>hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) ...[more]

PMID: 36932437

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Project description:BackgroundTreatment cost and high prevalence of Poly Cystic Ovarian Syndrome (PCOS) is a very challenging issue globally. Due to this reason; current study was conducted to determine pharmaco-economy of conventional and non-conventional treatments for the management of PCOS.MethodsProspective Cross-Sectional study was conducted in the metropolitan city of Karachi from January - December 2019. Primary data of 200 PCOS patients were collected from different hospitals and clinics. An instrument was used to collect data pertaining to the direct and indirect cost associated with the disease management. Collected data was analyzed by the tools for cost analysis and software called Statistical Package of Social Sciences (SPSS) - 22.ResultsIn Cost Minimization Analysis (CMA); Allopathic treatment [Mean cost/month: PKR:4479.32 ± 350.95 (USD:27.46 ± 2.15)], Herbal treatment [Mean cost/month: PKR:1527.78 ± 78.15 (USD:9.37 ± 0.48)], Combination treatment [Mean cost/month: PKR:2803.09 ± 654.22 (USD:17.18 ± 4.01)], and Homoeopathic treatment [Mean cost/month: PKR:976.95 ± 46.19 (USD:5.99 ± 0.28)]. Incremental cost/month for Allopathic treatment is 358%, Herbal treatment is 56%, Combination treatment is 187%. In Cost Effectiveness Analysis (CEA); Allopathic treatment (Incremental cost-effectiveness ratio/month: 1334.24), Herbal treatment (Incremental cost-effectiveness ratio/month: 936.41), Combination treatment (Incremental cost-effectiveness ratio/month: 1017.09). Due to lowest cost of Homeopathic treatment, cost of Homeopathic treatment was considered as a threshold value. In-direct cost/month of Allopathic treatment is PKR:593.33 ± 24.00 (USD:3.64 ± 0.15), Herbal treatment is PKR:307.84 ± 26.69 (USD:1.89 ± 0.16), Combination treatment is PKR:409.09 ± 45.63 (USD:2.51 ± 0.28) and Homoeopathic treatment is PKR:300.00 ± 26.39 (USD:1.84 ± 0.16).ConclusionThe most cost-effective is treatment is Homeopathic; Herbal treatment is second most cost-effective option for the treatment of PCOS. Lowest direct and indirect costs and short treatment duration collaboratively lessen the %incremental cost per year and incremental cost effectiveness ratio per year.

Project description:Premature ovarian failure (POF) is the pathological aging of ovarian tissue. We have previously established a cyclophosphamide-induced mouse POF model and found that cyclophosphamide caused significant damage and apoptosis of mouse ovarian granulosa cells (mOGCs). To systematically explore the molecular biologic evidence of cyclophosphamide-induced mOGC damage at the gene transcription level, RNA-Seqwas used to analyse the differences in mOGC transcriptomes between POF and control (PBS) mice. The sequencing results showed that there were 18765 differential transcription genes between the two groups, of which 192 were significantly up-regulated (log2 [POF/PBS] > 2.0) and 116 were significantly down-regulated (log2 [POF/PBS] < -4.0). Kyoto Encyclopedia of Genes and Genomes analysis found that the neuroactive ligand-receptor interaction pathway was significantly up-regulated and metabolic pathways were significantly down-regulated in the POF group. Gene Ontology analysis showed that the expression of plasma membrane, regulation of transcription and ion binding functions were significantly up-regulated in the POF group, while the expression of cell and cell parts, catalytic activity and single-organism process functions were significantly down-regulated. Finally, protein interaction analysis reveals that in the ovarian steroidogenesis pathway, three Cytochrome P450 family proteins-Cyp1a1, Cyp11a1 and Cyp2u1-interact with Fdx1 to form an interactive network. These three proteins were down-regulated in POF cells, suggesting that they are likely direct regulatory targets of cyclophosphamide. RNA-Seq high-throughput screening analysis demonstrated that cyclophosphamide damage to mOGCs was achieved through its impacts on multiple pathways and on the transcription activities of multiple target genes. Among them, the protein network consisting of the cytochrome P450 family Fdx1, Cyp17a1, Cyp11a1 and Cyp2u1 is a potential new biomarker of mOGC damage in POF in mice.

Dataset Information

Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients.

Background and aim

Experimental procedure

Results

Conclusion

Publications

Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients.

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