Kappaphycus alvarezii as a renewable source of kappa-carrageenan and other cosmetic ingredients.

Kappa-carrageenan is one of the most traded marine-derived hydrocolloids used in the food-and-beverage, pharmaceuticals, and personal care/cosmetics industries. K. alvarezii (previously known as Kappaphycus alvarezii) is arguably the most important natural producer based on annual production size and near-homogeneity of the product (i.e., primarily being the kappa-type). The anticipated expansion of the kappa-carrageenan market in the coming years could easily generate >100,000 MT of residual K. alvarezii biomass per year, which, if left untreated, can severely affect the environment and economy of the surrounding area. Among several possible valorization routes, turning the biomass residue into anti-photoaging cosmetic ingredients could potentially be the most sustainable one. Not only optimizing the profit (thus better ensuring economic sustainability) relative to the biofuels- and animal feed-routes, the action could also promote environmental sustainability. It could reduce the dependency of the current cosmetic industry on both petrochemicals and terrestrial plant-derived bioactive compounds. Note how, in contrast to terrestrial agriculture, industrial cultivation of seaweeds does not require arable land, freshwater, fertilizers, and pesticides. The valorization mode could also facilitate the sequestration of more greenhouse gas CO2 as daily-used chemicals, since the aerial productivity of seaweeds is much higher than that of terrestrial plants. This review first summarizes any scientific evidence that K. alvarezii extracts possess anti-photoaging properties. Next, realizing that conventional extraction methods may prevent the use of such extracts in cosmetic formulations, this review discusses the feasibility of obtaining various K. alvarezii compounds using green methods. Lastly, a perspective on several potential challenges to the proposed valorization scheme, as well as the potential solutions, is offered.

Cytotoxicity evaluation of phytochemicals from stingless bee (Tetragonula biroi) propolis.

Three prenylated flavonoids (1-3) were isolated from Tetragonula biroi propolis. The structures of the isolated compounds were characterized by NMR, IR, and UV spectroscopic and mass spectrometric analyses. The cytotoxicity activity of the crude extracts, fractions and the isolated compounds were established against four cell lines such as Caco-2, HeLa, MCF-7, and OVK-18. Among the tested compounds, compound 1 showed cytotoxicity activity against MCF-7 cell lines, whereas compound 2 showed good activity against Caco-2 and OVK-18 cell lines with IC50 values of 14.73 and 14.44, respectively. Moreover, compound 3 exhibited strong activity against OVK-18 cell lines. These findings contribute to the phytochemical understanding of the T. biroi propolis, and their cytotoxicity effects for future pharmaceutical purposes.

Antioxidant, anti-inflammatory and anti-acne activities of stingless bee (Tetragonula biroi) propolis.

We collected stingless bee propolis Tetragonula biroi in order to find materials for medicine and cosmetics applications from tropical rainforest resources. Even though this bee has some biological functions including a cancer cell line, hair growth promotion, asthma remedy, α-glucosidase enzyme inhibition, and antiviral action, the investigation on anti-acne has not been reported yet. This study was to focus on propolis Tetragonula biroi extracts and leads us to isolate active compounds for antioxidant, anti-inflammatory, and anti-acne. We used methanol to obtain the extract from this propolis and assayed it with antioxidants, anti-inflammation, and anti-acne. The extract showed strong activity in antioxidants by DPPH radical scavenging activity (82.31% in 6.25 µg/ml). Via a column chromatography and Reveleris PREP purification system, we isolated 3'-O-methyldiplacone, nymphaeol A, and 5,7,3',4'-tetrahydroxy-6-geranyl flavonol. These compounds showed potential biological activity with IC50 for antioxidant 6.33, 15.49, 17.32 µM; and antiinflammatory 121.54, 121.20, 117.31 µM. The isolated compounds showed anti-acne properties with properties 0.00, 14.11, and 13.78 mm for the inhibition zone (at a concentration of 1 µg/well), respectively. The results indicated that the propolis extract of Tetragonula biroi has the potential to be developed as a cosmetic agent; however, further work needs to be done to clarify its application.

Screening of Selected Stingless Bee Honey Varieties for ACE2-Spike Protein-Binding Inhibition Activity: A Potential Preventive Medicine Against SARS-Cov-2 Infection.

The broader objective of this study is to identify natural materials that might inhibit the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have focused on stingless bee honey, which has a unique taste that is both sweet and sour and sometimes bitter. We screened 12 samples of honey from 11 species of stingless bees using an angiotensin-converting enzyme 2 (ACE2)-spike protein-binding assay and phytochemical analysis. Ten of the samples showed inhibition above 50% in this assay system. Most of the honey contained tannins, alkaloids, flavonoids, triterpenoids, carotenoids and carbohydrates. Our findings in this in vitro study showed that honey from stingless bees may have a potent effect against SARS-CoV-2 infection by inhibiting the ACE2-spike protein-binding.

Cytotoxicity effect of honey, bee pollen, and propolis from seven stingless bees in some cancer cell lines.

Our effort to find new material for anti cancer from natural resources leads us to focus on stingless bee products such as honey, bee pollen, and propolis. The products were from seven stingless bees named Homotrigona fimbriata, Heterotrigona itama, Heterotrigona bakeri, Tetragonula sarawakensis, Tetragonula testaceitarsis, Tetragonula fuscobalteata, Tetragonula laeviceps. The stingless bee products were evaluated for their cytotoxicity effect on MCF-7, HeLa and Caco-2 cancer cell lines. This is the first time to be reported that the honey, ethanol extracts of bee pollen and propolis of H. fimbriata displayed more potent cytotoxicity than other stingless bee products. By chromatography and biological activity-guided fractionation, ethanol extract of propolis from H. fimbriata was fractionated and isolated its active compound named mangiferonic acid. Mangiferonic acid showed a cytotoxicity effect with IC50 values 96.76 µM in MCF-7, >110.04 µM in HeLa, and > 110.04 µM in Caco-2, respectively. These results exhibited the potential of ethanol extracts from propolis of H. fimbriata to be further developed for drug and experiments to verify the function are essential.

Anti-hypercholesterolemic effect of Zingiber montanum extract.

Background: Hypercholesterolemia, high cholesterol levels in the blood, can contribute to many forms of disease, most notably cardiovascular disease. Anti-hypercholesterolemic agents generally used for those conditions have several side effects for patients. Zingiber montanum , known locally as "bangle", belongs to the family Zingiberaceae and is a potential plants for alternative anti-hypercholesterolemic agents. This plant, from East Kalimantan, is used in traditional medicine for health problems caused by high cholesterol levels. The aim of this research was to find alternatives to anti-hypercholesterolemic agents, especially from natural sources. Methods: This study was an experimental study using 30 Wistar male white rats. Subjects were randomly divided into 6 groups (n=5): (1) normal control group; (2) high fat diet control group; (3) high fat diet with simvastatin; (4-6) high fat diet with Zingiber montanum extracts 100, 200, and 400 mg/kg. After 4 weeks of treatment, blood was collected from all groups, and plasma concentrations of triglycerides, total cholesterol, high density lipoproteins (HDL), and low density lipoproteins (LDL) were measured. Results: The results showed significant differences in total cholesterol (p=0.000), LDL (p=0.000) and triglycerides (p=0.001) in the high-fat diet group with Z. montanum extract, as compared to the high-fat diet control. Meanwhile, there were no significant differences in HDL levels (p=0.830) between the high-fat diet group and other groups. The results also showed significant differences in total cholesterol and LDLs for rats treated with Z. montanum extract, 100 mg/kg (p=0.000), 200 mg/kg (p=0.000), and 400 mg/kg (p=0.000) compared to the high-fat diet group. The result of Z. montanum 400 mg/kg also showed a significant reduction, not only for total cholesterol and LDLs, but also for triglycerides (p=0.030). Conclusion: It could be concluded that Z. montanum extracts have the potency to be further developed as a new natural source of the anti-hypercholesterolemic agents.

Melanogenesis inhibitors from Coix lacryma-jobi seeds in B16-F10 melanoma cells.

An adenine derivative, 9-ß-D-glucopyranosyl adenine, reported for the first time from a natural source, in addition to nine known compounds were isolated from the seeds of Coix lacryma-jobi. Their structures were elucidated based on extensive spectroscopic and chemical studies. The isolated compounds and the ethanol extract have been assayed for melanin inhibition using B16-F10 melanoma cell line. The results of our study suggested the potential use of Coix lacryma-jobi seeds as a skin whitening agent and reveal the seeds to be a rich source of important phytochemicals with melanogenesis inhibitory activity. Among the isolated compounds, coixol (2) and 2-O-ß-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (8) exhibited potent melanogenesis inhibitory activity with no obvious melanocytotoxicity. The rest of the compounds showed weak to moderate activity.

Inhibitory effects of isoflavonoids on rat prostate testosterone 5α-reductase.

Testosterone 5α-reductase inhibitors represent important therapeutic drugs for use against androgen-dependent diseases such as benign prostatic hyperplasia, male pattern baldness, and acne. We have searched for inhibitors of rat prostate testosterone 5α-reductase in the cultured broths of many kinds of soil bacteria, and have found that cultured soybean-casein digest broths of certain bacterial strains have a potent inhibitory effect on the enzyme. We tested 10 selected isoflavonoids, including isoflavones and O-methylated isoflavones, for inhibitory effects on rat prostate testosterone 5α-reductase to determine the important structural elements for inhibition of the enzyme. Genistein, biochanin A, equol, and 3',4',7-trihydroxyisoflavone showed considerably higher inhibitory effects whereas daidzein, formononetin, glycitein, prunetin, ipriflavone, and 4',7-dimethoxyisoflavone showed lower inhibitory effects. The IC(50) values of genistein, biochanin A, equol, 3',4',7-trihydroxyisoflavone, and riboflavin, a positive control, for rat prostate testosterone 5α-reductase were 710 µm, 140 µm, 370 µm, 690 µm, and 17 µm, respectively. Daidzein, genistein, biochanin A, formononetin, and equol are already known to be testosterone 5α-reductase inhibitors, but this is the first characterization of 3',4',7-trihydroxyisoflavone as an inhibitor of the enzyme.

The inhibitory effects of representative chalcones contained in Angelica keiskei on melanin biosynthesis in B16 melanoma cells.

In our effort to find new whitening agents, we evaluated the effects of representative chalcones [4-hydroxyderricin (1), xanthoangelol (2), xanthoangelol H (3), deoxyxanthoangelol H (4), and deoxydihydroxanthoangelol H (5)] contained in the stem of Angelica keiskei on tyrosinase and melanin formation in B16 melanoma cells. In addition, the antioxidant effects of these chalcones in ORAC and DPPH assays were also determined. Interestingly, all chalcones (1-5) inhibit melanin formation in B16 melanoma cells, with low cytotoxicity.

Validation of Eupatorium triplinerve Vahl leaves, a skin care herb from East Kalimantan, using a melanin biosynthesis assay.

In searching for a new material made from natural resources that could be used as a whitening agent, we focused on the plants used for skin treatment by the native people of East Kalimantan. The methanol extract of the leaves of Eupatorium triplinerve Vahl showed antimelanogenesis activity in a melanin biosynthesis assay. By activity-guided fractionation, 7-methoxycoumarin (1) was isolated as an active compound. The IC50 of 1 on mushroom tyrosinase was 2360 µM (L-tyrosine was used as the substrate) and above 2840 µM (L-DOPA was used as the substrate), respectively. Regarding melanin formation inhibition in B16 melanoma cells, the IC50 of 1 was 1780 µM with 83% cell viability at IC50. Based on these results, we validated that the leaf extract is in line with the traditional use of the Dayak tribe in East Kalimantan.

Artocarpus plants as a potential source of skin whitening agents.

Artocarpus plants have been a focus of constant attention due to the potential for skin whitening agents. In the in vitro experiment, compounds from the Artocarpus plants, such as artocarpanone, norartocarpetin, artocarpesin, artogomezianol, andalasin, artocarbene, and chlorophorin showed tyrosinase inhibitory activity. Structure-activity investigations revealed that the 4-substituted resorcinol moiety in these compounds was responsible for their potent inhibitory activities on tyrosinase. In the in vitro assay, using B16 melanoma cells, the prenylated polyphenols isolated from Artocarpus plants, such as artocarpin, cudraflavone C, 6-prenylapigenin, kuwanon C, norartocarpin, albanin A, cudraflavone B, and brosimone I showed potent inhibitory activity on melanin formation. Structure-activity investigations revealed that the introduction of an isoprenoid moiety to a non-isoprenoid-substituted polyphenol enhanced the inhibitory activity of melanin production in B16 melanoma cells. In the in vivo investigation, the extract of the wood of Artocarpus incisus and a representative isolated compound from it, artocarpin had a lightening effect on the skin of guinea pigs' backs. Other in vivo experiments using human volunteers have shown that water extract of Artocarpus lakoocha reduced the melanin formation in the skin of volunteers. These results indicate that the extracts of Artocarpus plants are potential sources for skin whitening agents.

Melanin biosynthesis inhibitory and antioxidant activities of quercetin-3'-O-beta-D-glucoside isolated from Allium cepa.

In the course of searching for new whitening agents, we have found that the methanol extract of dried skin of Allium cepa shows potent melanin biosynthesis inhibitory activity in B16 melanoma cells. Bioassay-guided fractionation led to the isolation of quercetin-3'-O-beta-D-glucoside (1) from the methanol extract of dried skin of A. cepa, which inhibited melanin formation in B16 melanoma cells with an IC50 value of 38.8 microM and mushroom tyrosinase with an IC50 value of 6.5 microM using L-tyrosine and 48.5 microM using L-dihydroxyphenylalanine as substrates, respectively. In addition, the antioxidant activity of 1 was evaluated in the oxygen radical absorbance capacity assay; it showed 3.04 micromol Trolox equivalents/mmol. 1 was shown to be a promising ingredient that could be useful for treating hyperpigmentation and for protecting against oxidative stress.

Biological activity and phytochemical analysis of three Indonesian medicinal plants, Murraya koenigii, Syzygium polyanthum and Zingiber purpurea.

Extracts of Indonesian medicinal plants, Murraya koenigii, Syzygium polyanthum, and Zingiber purpurea were investigated for their biological activity. The presence of phytochemicals, cytotoxicity, and antimicrobial and antioxidant activities were investigated. Parts of M. koenigii, S. polyanthum, and Z. purpurea were extracted with ethanol. The extracts were evaluated for antimicrobial activity using the disc diffusion method, while antioxidant activity was determined with a 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Cytotoxicity was investigated using the brine shrimp lethality test, and phytochemical screening was performed using a standard method. M. koenigii leaf extract exhibited the most activity in the test microorganism activity index (AI), 0.38-1.25, when compared with standard drugs. S. polyanthum ripened fruit displayed significant antioxidant activity (90%) in comparison to ascorbic acid (95%). Z. purpurea rhizome extract possessed the highest cytotoxic effect with a LC(50) of 52 µg/mL. Phytochemical analysis revealed that carbohydrate, tannin, alkaloid, steroid, triterpenoid, and flavonoid were present in the extracts of M. koenigii leaves and twigs, S. polyanthum leaves and ripened and unripe fruits, and Z. purpurea rhizome, while saponin was only present in the S. polyanthum ripened fruit extract. Our work revealed that the M. koenigii leaves, S. polyanthum ripened fruit, and Z. purpurea rhizome extracts have potential as sources of new antimicrobial, antioxidant, and cytotoxic compounds, respectively.

Tyrosinase inhibitory effect of quercetin 4'-O-ß-D-glucopyranoside from dried skin of red onion (Allium cepa).

In an effort to find a new whitening agent, we focused our attention on Allium cepa (red onion). Based on biologically guided fractionation using mushroom tyrosinase, quercetin 4'-O-ß-D-glucopyranoside was isolated from the dried skin of A. cepa. Quercetin 4'-O-ß-D-glucopyranoside showed tyrosinase inhibitory activity using L-tyrosine or L-DOPA as a substrate, with IC(50) values of 4.3 and 52.7 µM, respectively. Based on the results obtained, the dried skin of red onion possesses ingredients with potential for skin-whitening cosmetics with anti-tyrosinase activity.

Inhibitory components from the buds of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells.

In the course to find a new whitening agent, we evaluated the methanol extract from bud of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells. Eugenol and eugenol acetate were isolated as the active compounds and showed melanin inhibition of 60% and 40% in B16 melanoma cell with less cytotoxicity at the concentration of 100 and 200 µg/mL, respectively. Furthermore, an essential oil prepared from the bud of clove, which contain eugenol and eugenol acetate as dominant components, showed melanin inhibition of 50% and 80% in B16 melanoma cells at the concentration of 100 and 200 µg/mL, respectively.

Cytotoxic effect of artocarpin on T47D cells.

In our screening projects for anticancer agents from natural resources, artocarpin [6-(3-methyl-1-butenyl)-5,2',4'-trihydroxy-3-isoprenyl-7-methoxyflavone] isolated from wood of jack fruit (Artocarpus heterophyllus) showed potent cytotoxic activity on human T47D breast cancer cells. The mode of action of artocarpin was evaluated by its effect on cell viability, nuclear morphology, cell cycle progression, expression of protein markers for apoptosis, and mitochondrial membrane potential (Delta psi m). These results showed that artocarpin caused a reduction of cell viability in a concentration-dependent manner and an alteration of cell and nuclear morphology. Moreover, the percentage of the sub-G1 phase formation was elevated dose-dependently. Artocarpin induced activation of caspase 8 and 10 as indicated by stronger signal intensity of cleaved-caspase 8 and weaker signal intensity of caspase 10 markers detected after artocarpin treatment. In addition, we also noticed the activation of caspase 3 by artocarpin. There were negligible changes in mitochondrial membrane potential (Delta psi m) due to artocarpin treatment. All together, these data indicated that artocarpin induced apoptosis in T47D cells possibly via an extrinsic pathway.

3-Prenyl luteolin, a new prenylated flavone with melanin biosynthesis inhibitory activity from wood of Artocarpus heterophyllus.

In our efforts to find new whitening agent from natural resources, we focused on wood of Artocarpus heterophyllus which shows anti-melanogenesis activity. By activity-guided fractionation of A. heterophyllus wood extract, a new prenylated flavonoid, 3-prenyl luteolin (1) was isolated. The IC(50) of mushroom tyrosinase inhibitory activity of 1 was 76.3 microM. The results of the comparison with that of luteolin showed the prenyl substituent at C-3 position of 1 play an important role for revealing tyrosinase inhibition. In melanin formation inhibition on B16 melanoma cells, IC(50) of 1 was 56.7 microM with less cytotoxicity.

Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown in Indonesia.

An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae) collected from East Kalimantan, Indonesia, was tested for its antidermatophyte and antimelanogenesis activity. Antifungal assay-directed fractionation of the n-hexane-soluble fraction of the methanolic extract of the bulb of E. americana led to the isolation of 1 as an active compound. The compound was identified as the naphthoquinone eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80 microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1 displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared with arbutin, a commercial skin-whitening agent. The results showed the high potential of 1, an active compound from E. americana, to be applied as an antidermatophyte and antimelanogenesis agent.

Isoprenoid-substituted flavonoids from wood of Artocarpus heterophyllus on B16 melanoma cells: cytotoxicity and structural criteria.

As a result of cytotoxicity-guided fractionation, nine flavonoids, artocarpin (1), cudraflavone C (2), 6-prenylapigenin (3), kuwanon C (4), norartocarpin (5), albanin A (6), cudraflavone B (7), brosimone I (8) and artocarpanone (9) were identified from the methanol extract of the wood of Artocarpus heterophyllus, known commonly as Nangka in Indonesia. A structure-activity investigation of the effect of these isolated compounds (1-9) and structurally related compounds on B16 melanoma cells indicated that isoprenoid moiety substitutions in flavonoids enhance their cytotoxicity, and that the position of attachment and the number of isoprenoid-substituent moieties per molecule influence flavonoid cytotoxicity.