Dual effects of Camellia sinensis and Andrographis paniculata on hyperglycemia and infection in Drosophila

Abstract

The coexistence of hyperglycemia and infectious diseases represents a critical global health challenge, particularly in resource-limited settings where it amplifies disease severity and complicates treatment approaches. Medicinal plants such as Camellia sinensis and Andrographis paniculata have gained recognition for their antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for addressing this double health burden. The aim of this study was to establish a preclinical model of hyperglycemia and infection (HI model) using Drosophila melanogaster and to investigate the therapeutic potential of C. sinensis and A. paniculata extracts in alleviating the burden associated with the HI condition. In this study, the HI model was established by simultaneously exposing D. melanogaster larvae to a high-concentration sucrose solution and Staphylococcus aureus for 24 hours. The larvae were then transferred to a high-sucrose diet supplemented with C. sinensis or A. paniculata extracts. Survival assays and molecular analyses were subsequently performed to evaluate the outcomes. Our findings revealed that the combination of hyperglycemia and infection significantly reduced survival rates in the Drosophila model. However, treatment with 1.25% C. sinensis and A. paniculata extracts notably improved survival, attributed to their antibacterial activity and regulation of key molecular pathways involved in immune responses, metabolic balance, and endogenous antioxidant defenses. These findings validate the utility of D. melanogaster as a model organism for investigating the double burden of HI. Furthermore, the study offers compelling evidence of the dual therapeutic potential of C. sinensis and A. paniculata in mitigating the detrimental effects of this condition. Overall, this research underscores the significant promise of plant-derived compounds in managing HI and paves the way for future studies to explore their underlying mechanisms and potential clinical applications.

Keywords: Andrographis paniculata; Camellia sinensis; Drosophila; hyperglycemia; infection.

Figure 1.

Study design, timeline, and settings. The research timeline consisted of key steps, including the establishment of the hyperglycemia and infection (HI) model, survival and developmental toxicity evaluations during extract administration, and molecular analysis (A). The establishment of the HI model was initiated by generating separated hyperglycemia and infection model groups, which were optimized to create the HI model using a 96-well plate (B). After the HI model was successfully developed, experiments were performed to evaluate the potential of Camellia sinensis (CS) and Andrographis paniculata (AP) extracts in mitigating the adverse effects of hyperglycemia and infection in this model. AP: Andrographis paniculata; CS: Camellia sinensis; HI: hyperglycemia and infection; HSD: high sugar diet; PBS: phosphate-buffered saline.

Figure 2.

Impacts of elevated sucrose concentration and bacterial load on Drosophila survival. Increasing sucrose concentration (A) and bacterial load (B) lead to a reduction in the survival rate of Drosophila larvae. Meanwhile, simultaneous increases in sucrose concentration and bacterial load result in decreased survival of Drosophila (C). The impaired regulation of dilp2 (D) and drs (E) is associated with reduced survival in the hyperglycemia and infection (HI) model. NS: non-significant; significant at *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Figure 3.

Effects of Camellia sinensis and Andrographis paniculata extracts administration on Drosophila larvae. Developmental progression from larvae to pupae (A, C) and pupae to adult flies (B, D) following treatment demonstrated that both extracts at 1.25% concentration were relatively safe and provided protective benefits, enhancing survival in the hyperglycemia and infection (HI) model. Significant at *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Figure 4.

Administration of Camellia sinensis (CS) and Andrographis paniculata (AP) extracts positively modulated the interplay between immune and metabolic activities in the Drosophila model of hyperglycemia and infection (HI). Notable modulation was observed in the expression of NF-κB-dependent immune pathways (A-B), whereas the JAK/STAT pathway (C) remained unaffected. Furthermore, the extracts significantly impacted insulin-associated metabolic pathways (D), underscoring their dual role in enhancing immunity and metabolic regulation. NS: non-significant; significant at *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Figure 5.

Modulation of endogenous antioxidant gene expression of gst (A), sod1 (B), sod2 (C), and cat (D) by Camellia sinensis (CS) and Andrographis paniculata (AP) extracts in the Drosophila model of hyperglycemia and infection (HI). C. sinensis extract promotes the upregulation of gst (A), while A. paniculata extract enhances the expression of sod1 (B) and cat (D), emphasizing their potential to alleviate oxidative stress caused by hyperglycemia and infection. NS: non-significant; significant at *p < 0.05 and **p < 0.01.

Figure 6.

Potential protective mechanisms of Camellia sinensis (CS) and Andrographis paniculata (AP) in the Drosophila model of hyperglycemia and infection (HI).