Despite extensive research in chemotherapy, global cancer concerns persist, exacerbated by the challenge of drug resistance, which imposes economic and medical burdens. Natural compounds, particularly secondary metabolites from medicinal plants, present promising avenues for overcoming cancer drug resistance due to their diverse structures and essential pharmacological effects. This review provides a comprehensive exploration of cancer cell resistance mechanisms and target actions for reversing resistance and highlights the in vitro and in vivo efficacy of noteworthy alkaloids, flavonoids, and other compounds, emphasizing their potential as therapeutic agents. The molecular properties supporting ligand interactions are thoroughly examined, providing a robust theoretical foundation. The review concludes by discussing methods including quantitative structure-activity relationships and molecular docking, offering insights into screening potential candidates. Current trends in clinical treatment, contributing to a holistic understanding of the multifaceted approaches to address cancer drug resistance are also outlined.

Houttuynia cordata Thunb. has long been widely used as a daily vegetable and traditional medicine. The flavonoid component of H. cordata has plenty of pharmacological effects, such as antibacterial, anti-inflammatory, and antioxidant. In this study, we applied the aqueous two-phase system (ATPS) combined with ultrasonic extraction for extracting H. cordata leaves. We optimized the extraction process to improve the extraction efficiency of the two flavonoids, hyperin and quercitrin, by Surface Method Response - Central Composite Design (RSM-CCD). Next, we investigated the antibacterial ability of H. cordata ATPS extract from optimal conditions against two bacterial strains, Cutibacterium acnes and Staphylococcus epidermidis. The results showed that using 10% (NH₄)₂SO₄ and 35% ethanol for ATPS extraction resulted in the highest hyperin and quercitrin contents. From the RSM-CCD results, the optimal extraction conditions were determined to be ultrasonic extraction at 50 °C for 30 min, giving results consistent with the predicted model and obtaining hyperin and quercitrin contents at 1.5681 ± 0.0114 and 4.6225 ± 0.0327 mg/g, respectively.Furthermore, ATPS extract has excellent antibacterial activity with a minimum inhibitory concentration (MIC) value of 250 μg/mL on both C. acnes and S. epidermidis. This MIC is significantly lower than the H. cordata ultrasound-assisted (UA) extract, with MICs of 1500.00 and 156.25 μg/mL on C. acnes and S. epidermidis, respectively. In addition, the results from the disk diffusion assay also showed that ATPS extraction has superior internal antibacterial activity with a zone of inhibition diameter at 250 μg/mL of 8.67 ± 1.15 and 5.00 ± 2.00 mm. Meanwhile, those of UA extract on C. acnes is 5.67 ± 1.53 mm (at 1500 μg/mL), and on S. epidermidis is 1.34 ± 0.58 mm (at 156.25 μg/mL). To sum up, our research highlights the potential of H. cordata ATPS extracts as the starting material for topical preparations for effectively treating acne.

Drug resistance is one of the leading causes attributed to the failure of cancer treatment by chemotherapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating gene expression in cell defense against oxidative stress or hazardous factors. Taking advantage of this feature, Nrf2 also serves as the bodyguard for both normal and cancer cells. Many pieces of evidence have reported that inhibiting Nrf2 activity in cancer cells can reverse chemotherapy drug resistance. In addition, secondary metabolites from medicinal plants have been reported to inhibit Nrf2 activity in the in vitro study. This study aimed to preliminarily investigate fractions from medicinal herbs that inhibit Nrf2 activity in Huh7 liver cancer cells, thereby establishing a basis for subsequent isolation and extraction processes. Sub-fractions from five medicinal plants have been evaluated the Nrf2 inhibitor activity on Huh7 cells through luciferase-reported genes assay. Thin-layer chromatography (TLC) was also performed to quantify the extracts' main phytochemistry components. Combining the half-maximal inhibitory concentration (IC₅₀) and half-maximal cytotoxicity concentration (CC₅₀) enables us to determine which extracts have the potential for further isolation steps. Ten over 30 crude extracts and sub-fractions showed the inhibition of Nrf2 activity with the percentage ranging from 30 to 97 %. The methanol and n-hexane sub-fractions from Helicteres hirsuta Lour. leaves showed the strongest inhibition ability on Nrf2 activity with the IC₅₀ = 20.98 ± 3.67 and 42.22 ± 2.10 μg/mL, respectively. The TLC results showed the presence of steroids and terpenoids in the promising sub-fractions. Combining the TLC results with the in vitro screening on Nrf2 activity screening of medicinal plants, the outcomes suggest the steroids and terpenoids in the methanol extract and hexane sub-fraction from Helicteres hirsuta Lour. leaves show promise towards inhibiting Nrf2 activity in liver cancer cell lines without toxicity in the normal cells.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and is the leading cause of cancer mortality in Vietnam. Our study aims to discover the partial extracts with the potential cytotoxic effects on HCC cells from the different parts of 24 Vietnamese medicinal plants traditionally used in liver cancer treatment. Out of 52 crude methanol extracts, we found that Luvunga scandens leaves, Hyptis suaveolens roots, and Solanum torvum leaves showed the notable cytotoxic effects against HCC cells. After that, we carried out partial extract of the three methanol extracts with ethyl acetate, water, n-hexane, and 90% methanol. The cytotoxic activity on Huh-7 HCC cells, antioxidant capacity, and total flavonoids content (TFC) of each partial extraction were determined. Methanol, ethyl acetate, and 90% methanol extracts showed moderate to strong cytotoxicity activity against Huh-7 HCC cells. Notably, the ethyl acetate and 90% methanol extract from H. suaveolens roots with high TFC values and strong antioxidant capacity could be promising sources of novel therapeutic modalities for HCC treatment. For the leaves of L. scandens and S. torvum, the ethyl acetate extract showed high TFC value and promising anti-HCC activity, therefore recommended further studies.