Current Bioactive Compounds - Volume 21, Issue 6, 2025

Hepatocellular carcinoma (HCC) poses a threat to human health due to several risk factors associated with one’s lifestyle, including liver cirrhosis, alcohol intake, obesity, exposure to aflatoxin, hepatitis B and/or C virus infection, non-alcoholic steatohepatitis (NASH), diabetes and many other factors. The treatment of HCC involves several distinct approaches, including significant advancement in surgical interventions. Given the toxicity of conventional medicines or the need for a suitable approach focusing on the stages of HCC progression, the current treatment is not very effective, which brings a significant focus on improving alternative-targeted approaches as anti-HCC moieties.

Therefore, this review provides an update on how the phytoconstituents exhibit their anti-HCC effect by intervening in the control of autophagy.

This study conducted a thorough literature search on hepatocellular carcinoma (HCC), autophagy, and phytoconstituents. The search was performed using multiple search engines and the main keywords, and only English publications published before April 2023 were included.

One of the various molecular-mediated mechanisms used in cancer therapies is ‘Autophagy,’ a metabolic process whereby cellular stress causes damaged cells to be cleared out to preserve cellular homeostasis and provide cells with the nutrients they need to survive. Because of its dual activity as a tumor suppressor or tumorigenesis, autophagy-mediated manipulation could be a promising option for treating cancer.

Phytochemicals derived from natural sources offer an antitumorigenic effect and reduce the probability of HCC by regulating autophagy-mediated mechanisms and functioning as tumor suppressors.

In recent years, bioenergy has received a lot of attention from a technical point of view due to its ability to use reversible resources and its applicability worldwide. Biodiesel is a non-toxic, safe, renewable, and degradable fuel that is obtained from natural sources, such as vegetable oils, food waste oils, animal fats, algae, and microorganisms. This study aimed to optimize the lipid production of Rhodosporidium toruloides as a biofuel from different substrates.

In this experimental laboratory study, after lipid extraction from Rhodosporidium toruloides CECT1137, cell biomass, nitrogen, and sugar consumption were measured according to the Bly and Dyer method. Then, using gas chromatography, the produced lipid compounds were identified, and lipid production was optimized by the one-factor method (type of nitrogen source and KH2PO4) and the Taguchi method (carbon and nitrogen source, temperature, pH, centrifuge, and time). Finally, the feasibility of mutation was investigated using UV to optimize lipid production.

The amount of lipid produced by Rhodosporidium toruloides was 4.95 g/l, which, after optimization by the Taguchi method, reached 8.54 g/l. Cell biomass, residual nitrogen, and consumed sugar were measured as 14.05, 0.19, and 28.85 g/l, respectively. Optimal production conditions were estimated by Taguchi, including 80 g/l carbon source, 1 g/l nitrogen source, 25°C, pH = 5.5, centrifuge at 180 rpm, and 96 hours. Most lipids produced were oleic acid and palmitic acid. Lipid production increased after UV exposure.

The results showed that Rhodosporidium toruloides can accumulate a significant amount of lipid in its cells and can be a good alternative to plants and other sources of fuel production.

The natural triterpenoid molecule betulinic acid (BA) has many biological and therapeutic uses, one of which is the relief from asthma symptoms. The purpose of this study was to assess BA effectiveness in treating bronchial asthma and to perform a molecular docking study to find the binding energy of BA with β-adrenoceptor.

Bacopa monnieri leaf extraction was performed in a soxhlet apparatus using ethanol as a solvent. Budesenoid was used as a standard drug. AutoDock vina in PyRx 0.8 was used for the molecular docking investigation. An acute toxicity study was conducted according to OECD guideline 425. A guinea pig model of asthma called anaphylactic microshock was used to ascertain the antiasthmatic efficacy of the test drug. Antiasthmatic activity was determined by grouping the animals into four groups, each containing six animals. Group 1 was the control group that received only vehicles. Group 2 was the standard group that received budesenoid. Group 3 was the test group that received B. monnieri extract. Group 4 was the test group received BA.

In terms of binding affinity, BA had a value of -7.45 kcal/mol, showing binding with β-adrenoceptor. A molecular docking study showed that BA was bound to the hydrophobic cavity of LOX-5, and the formation of hydrogen bonds altered the micro-environment and structure of LOX-5. This resulted in a reduction in enzyme activity. The mean pre-convulsion time for the test drug was 506.66 in comparison to the control group, as observed in the guinea pig model of asthma.

BA was found to be effective in reducing anaphylaxis in animal models. Thus, it may be used as an alternative drug in treating asthma after clinical trials. However, a molecular docking study verified that BA had a prospective target on the desired receptor for further therapeutic development.

As per the literature survey, the pyrimidine-based molecules display prominent antibacterial, anti-inflammatory, antioxidant, anticancer, analgesic, anticonvulsant, anti-tubercular and antimalarial properties. The biological relevance of pyrimidine-based pharmacophore structures encourages us to synthesize some novel imines derived from 2-amino pyrimidine and substituted benzaldehydes.

The present communication describes the synthesis of six imines 3a-f derived from 2-aminopyrimidine. The tri-potassium phosphate catalyst used in the current study optimizes the microwave-assisted synthesis of these novel Schiff bases. The reported method for the synthesis of imines is found to be eco-friendly in terms of the effective use of catalyst Al2O3-K3PO4 with microwave in the synthesis of pyrimidine-based Schiff bases.

Different spectroscopic methods, such as ¹H NMR, IR, GCMS and elemental analysis, were used to determine the structure of all synthesized Schiff bases. Further, the imines 3a-f were screened for antibacterial properties to check their inhibitory potency against E. coli and S. aureus.

The biological potency of imines 3a-f was also studied for their antioxidant and in-vitro anti-inflammatory activity. The obtained results reveal that Schiff base 3c showed potent anti-inflammatory activity with a 31.538% ± 2.055 inhibition of inflammation. Moreover, the synthesized imines 3a-f have been screened and studied for their antioxidant activity by DPPH and nitric oxide radical scavengers. Some of these, like 3c, show 15.98 ± 2.64 potency to scavenge DPPH radicals as compared to standard. In the antimicrobial investigation, most of the Schiff bases showed good inhibitory activity against various tested pathogens. The current study, therefore, contributes to investigate a new class of imines with structurally modified anti-inflammatory and antioxidant drugs.

The outcome of the study revealed that compound 3c showed promising anti-inflammatory activity with 31.538 ± 2.055 inhibition of inflammation. All imines display antibacterial potency in compounds 3a, 3b, 3c, and 3f. The antibacterial properties of these imines are attributed to -OCH3, -OH and -Br as primary bioactive substituents present in the moiety of imines, which enhance inhibitory properties against tested pathogens. The antioxidant scavenging activity of imines indicates that compounds 3a, 3c, 3d, and 3f represent better anti-oxidants as DPPH scavengers than standard ascorbic acid.

The use of medicinal plant compounds for cancer treatment has been considered since ancient times. This systematic study aimed to conduct a review on the effects of medicinal plant extracts on oral cancer cell lines in vitro.

In this systematic study, articles were searched in databases, including PubMed, Google Scholar, ScienceDirect, Web of Science, and Scopus, using keywords as “herbal drugs”, “medicinal plants”, “extract”, “essence”, “oral cancer”, “in vitro”, and “clinical trials”.

After searching the articles according to inclusion and exclusion criteria, removing duplicates, and reviewing full-text articles, the researchers entered the data of all the collected articles into Endnote X9. Initially, 14,650 studies were identified, but after applying the inclusion/exclusion criteria, 21 studies were selected.

According to the inclusion and exclusion criteria, 21 studies have been selected. The study's findings have revealed that medicinal plants have the potential to inhibit the growth of oral cancer cells, making them a promising candidate for further research on cancer treatment.

The study aimed to assess the effectiveness of Selaginella plana in treating diabetes. The plant components were assessed using ethanol as a solvent. To determine whether the plant extracts included any secondary metabolites, a phytochemical screening was performed.

The quantities of total phenolic and total flavonoid were determined using plant extracts in ethanolic, chloroform, petroleum, and water solutions. Experimental animals were used to evaluate the antioxidant properties of plant extracts. Thus, the study was further processed to evaluate antidiabetic activity using ethanolic and aqueous extracts. Glucose levels were measured using an oral glucose tolerance test (OGTT).

The percentage yield of ethanol, chloroform, petroleum ether, and aqueous extract were 19.22 g, 11.01 g, 6.44 g, and 15.76 g, respectively. The ethanolic and aqueous extracts showed the presence of most of the phytoconstituents like alkaloids, flavonoids, carbohydrates, tannins, phytosterols, glycosides, proteins, and gum. TPC values were high for ethanolic extract of the fern S. plana, which was 54.34 mg GAE/g for ethanolic extract. However, the TFC value was 264.51 mg QE/g for ethanolic extract. Normalisation of insulin levels and restoration of blood glucose levels were both demonstrated by the plant extract.

It can be concluded from the study that ethanolic extract of S. plana was effective against STZ-induced diabetes. S. plana may be an alternative drug in treating diabetes after clinical trials.

Dermatophytes are a class of fungi that invade keratinized tissues in humans and other animals, including hair, skin, and nails, causing dermatophytoses. The high cost of therapy, side effects of drugs, and occasionally microbial resistance to synthetic drugs are some of the issues that have prompted efforts to find new medicines. This research aimed to study the antifungal properties of ethanolic and methanolic extracts of Rumexacetosella, Teucrium polium, and Glycyrrhiza glabra plants against Microsporum canis,Microsporum gypseum, and Trichophyton mentagrophytes and to ascertain the phenol content of these plants.

Following the collection and identification of R. acetosella, T. polium, and G. glabra for this descriptive comparative study, they were washed and dried in the shade. Next, the Soxhlet apparatus was used to obtain methanolic and ethanolic extracts from these plants. The antifungal activity of these extracts was examined in vitro against M. canis, M. gypseum, and T. mentagrophytes using the diffusion and agar dilution method according to CLSI guidelines. The Minimum Inhibitory Concentration (MIC) and the Minimum Fungicidal Concentration [MFC] of the extracts were also determined compared to griseofulvin. Additionally, the phenol content of these extracts was measured by an optical spectrophotometer.

The methanolic extract of T. polium at 200 mg/ml led to the maximum inhibition zones of T. mentagrophytes PTCC 5054, M. canis PTCC 5069, and M. gypseum PTCC 5070 that were 23.41, 23.45, and 25.30 mm, respectively. The highest growth rates of T. mentagrophytes, M. canis, and M. gypseum in agar dilution method were found in 2.5 mg/ml of G. glabra ethanolic extract at 19.07, 18.32, and 17.81 mm, respectively. The smallest growth of T. mentagrophytes, M. canis, and M. gypseum were observed in the plate containing 40 mg/ml of the methanolic extract of T. polium, with 5.62, 3.72, and 5.41 mm diameters, respectively. MIC was less than 6.25 mg/ml for methanolic extract of T. polium. The tannic acid in the ethanolic and methanolic extracts of T. polium, R. acetosella, and G. glabra were 227.33 and 482.89 μg/ml, 94 and 475.48 μg/ml, and 27.33 and 60.67 μg/ml, respectively.

The results revealed that methanolic extracts of the plants under study, particularly T. polium, had a stronger inhibitory impact than ethanolic extracts. Following rigorous toxicity testing and in vivo research, methanolic extracts of these plants may prove to be effective options as adjuvants or alternatives to chemical drugs.

The pharmacological significance of 5-hydroxy-3,7,4'-trimethoxy flavone (5HTMF), a flavonoid isolated from Cleome gynandra L. (Capparidaceae), in mononuclear lymphocytes of patients with Rheumatoid Arthritis (RA) has been well-documented. In previous studies, the anti-inflammatory and anti-arthritis activity of CWF was reported.

However, there is a lack of information on the toxicity of 5HTMF. This study aimed to assess the embryonic toxicity of 5HTMF on zebrafish embryos, using dexamethasone as a standard for liver toxicity. At 12 hours post fertilization (hpf), no significant toxicity from 5HTMF was observed on allantoic membrane development.

By 24 hpf, 20% of embryos showed minor changes in tail development at a 100 μM concentration of 5HTMF, while dexamethasone (10 μM) disrupted the allantoic membrane in 61.11% of embryos. In the liver toxicity assay, 5HTMF did not show any significant toxicity.

At 48 hpf, dexamethasone exhibited substantial toxicity at a concentration of 10 μM. In conclusion, the findings suggest that 5HTMF may be a safe and non-toxic dietary supplement for treating chronic inflammatory conditions such as RA.

The marine clam Anadara compacta is a common bivalve mollusk found in many coastal regions in the Philippines but is underutilized despite its nutritional value. The study aimed to determine the bioactive potential of A. compacta for its optimum utilization as a promising novel source of metabolites with pharmaceutical potential.

The proposed approach in the profiling of metabolites included solvent extraction, fractionation by C18 column chromatography and liquid chromatography-mass spectrometry (LC-MS)-guided profiling of the active fractions. Biological investigations comprised cytotoxicity, antibacterial and antioxidant activity assessments.

The methanol solvent fractions obtained from the water layer of A. compacta contained various chemical constituents namely alkaloids, terpenoids, linear and cyclic peptides, cytotoxic macrolides, among others based on LC-MS analysis. The 100% methanol fraction showed the highest inhibitory effect against MCF-7 human breast cancer cells among other fractions with an IC50 value of 118.57 ± 0.14 µg/mL. Moreover, the fractions also inhibited the growth of Gram-positive and Gram-negative bacterial strains tested and showed strong antioxidant potential as a 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenger.

Our findings demonstrated the effectiveness and complementary nature of LC-MS metabolites profiling in conjunction with bioassays for the identification of bioactive constituents in the marine clam A. compacta. The bioactive fractions from A. compacta may be utilized as useful ingredients for developing pharmaceutical and nutraceutical applications.

Vietnam has been heavily endemic for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, which are associated with cirrhosis and liver cancer. Combined with the high prevalence of alcohol consumption as a risk factor, these factors contribute to liver cancer being the leading cause of cancer-related mortality in the country.

Despite the help of computers, discovering new antitumor agents remains challenging due to the complexity and variety of targets involved. Thus, traditional methods for identifying antitumor compounds remain valuable. These approaches aim to synthesize and evaluate new derivatives for potential antitumor activity. The quinazoline scaffold has attracted considerable attention for its broad antitumor activity, low toxicity, high efficacy, and distinct mode of action. Additionally, morpholine derivatives have been reported as potential antitumor agents. Incorporating both the quinazoline pharmacophore and morpholine ring into a single molecular structure is expected to yield new compounds with strong activity, potentially serving as effective antitumor agents against the HEP-G2 cell line. In this work, Seven novel hybrid compounds (3a-g), in which quinazolin-4(3H)-one ring is incorporated into morpholine ring by the reaction of the 3-aryl-2-mercaptoquinazolin-4(3H)-ones (2a-g) with 4-(2-chloroethyl)morpholine, were synthesized. The intermediates (2a-g) were prepared by the reaction of anthranilic acid with carbon disulfide and appropriate aromatic amines in an alkaline medium.

The structural features of these products were studied by their IR, 1H-NMR, 13C-NMR, and HR-MS spectral data. In addition, the structure of one hybrid compound (3a) was determined by X-ray crystallography. Subsequently, their antitumor activities against the HEP-G2 human cell line were performed and reported. Based on the collected data, none of the synthesized compounds showed significant activity as potential antitumor agents.

These results may be influenced by factors such as molecular polarity and/or the specific target tested. Further investigation and structural modifications are needed for a more comprehensive understanding.

Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin-E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated.

The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin-E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin-E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined.

The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 µg/ml. LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors.

These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.