(−)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyc... more (−)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.
High telomerase activity (TA) is detected in most cancer cells; and thus, TA inhibition by drug o... more High telomerase activity (TA) is detected in most cancer cells; and thus, TA inhibition by drug or dietary food components is a new strategy for cancer prevention. In this report, we examined the effects of fourteen natural or synthetic compounds on TA in human lung adenocarcinoma A549 cells. The results demonstrated that some of the tested compounds inhibited TA, being 2'-hydroxy-2,3,4',6'-tetramethoxychalcone (HTMC) was the most potent among tested. In A549 cells, HTMC also inhibited the cell proliferation, decreased the expression of human telomerase reverse transcriptase (hTERT) and sequentially reduced the hTERT promoter. In soft agar assay HTMC treatment reduced the colony formation of A549 cells. Cellular fractionation and immunofluorescence assay demonstrated that there was no translocation of hTERT from nuclei to cytoplasm. Further studies revealed that the release of Ca(2+) was the underlying mechanism of suppressed TA and hTERT transcription in A549 cells exposed to HTMC. These in vitro data support the development of HTMC as a therapeutic agent for cancer complications.
Canadian Institute of Food Science and Technology journal, Oct 1, 1988
Abstract Previously reported rapeseed protein isolation methods resulted in low yields or low pro... more Abstract Previously reported rapeseed protein isolation methods resulted in low yields or low protein purity. The isolates often had an unpleasant taste or dark colour, and the levels of glucosinolates, phytates or both in these products were a source of concern. A novel processing scheme was developed which included extraction with an aqueous sodium hexametaphosphate or sodium hydroxide solution, ultrafiltration, isoelectric precipitation at pH 3.5, and diafiltration. An isoelectric protein fraction and a soluble protein fraction were produced. Up to 71.2% of the nitrogen was recovered in the isolates. The protein content of the isoelectric protein and soluble protein isolate was close to or higher than 90% (N × 6.25). A phy-tate content of less than 2% was achieved. These isolates were free of glucosinolates.
Response surface methodology (RSM) was employed to study the effect of culture medium on the prod... more Response surface methodology (RSM) was employed to study the effect of culture medium on the production of lovastatin in mixed solid-liquid state (or submerged) cultures by Monascus ruber. The maximal lovastatin yield (131 mg/L, average of three repeats) appeared at the region where the respective concentrations of rice powder, peptone, glycerin, and glucose were around 34.4 g/L, 10.8 g/L, 26.4 ml/L, and 129.2 g/L, respectively. The optimized medium resulted in a significant increase of lovastatin yield, as compared with that obtained by the fermentation of many other M. ruber species.
Applied Biochemistry and Biotechnology, Mar 8, 2022
4-Acetylantroquinonol B (4-AAQB) was identified in the rare fungus Antrodia cinnamomea and has be... more 4-Acetylantroquinonol B (4-AAQB) was identified in the rare fungus Antrodia cinnamomea and has been proven to be a potential therapeutic agent for cancer treatment. But the extraction of 4-AAQB from the fruit body led to a low yield and limited its further application in the pharmaceutical field. In this work, 4-AAQB production was enhanced in the submerged fermentation by the combination of exogenous additives, surfactants with the in situ extractive fermentation. 4-Methylbenzoic acid was proven to be an efficient additive for the accumulation of 4-AAQB by Antrodia cinnamomea, while 2% (w/v) Tween-80 added on the first day as surfactant and 30% (w/v) oleic acid added on the sixteenth day as extractant were the most available couples for 4-AAQB production in the in situ extractive fermentation. The combination of these multiple strategies resulted in the yield of 4-AAQB to 17.27 mg/g dry cell weight with a titer of 140 mg/L, which was the highest titer of 4-AAQB reported so far. It showed that the combination of these strategies had a significant promotion on 4-AAQB production by A. cinnamomea, which laid a good foundation for its large-scale production and also provided a viable method for the cultivation of other rare fungi.
(−)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyc... more (−)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.
High telomerase activity (TA) is detected in most cancer cells; and thus, TA inhibition by drug o... more High telomerase activity (TA) is detected in most cancer cells; and thus, TA inhibition by drug or dietary food components is a new strategy for cancer prevention. In this report, we examined the effects of fourteen natural or synthetic compounds on TA in human lung adenocarcinoma A549 cells. The results demonstrated that some of the tested compounds inhibited TA, being 2'-hydroxy-2,3,4',6'-tetramethoxychalcone (HTMC) was the most potent among tested. In A549 cells, HTMC also inhibited the cell proliferation, decreased the expression of human telomerase reverse transcriptase (hTERT) and sequentially reduced the hTERT promoter. In soft agar assay HTMC treatment reduced the colony formation of A549 cells. Cellular fractionation and immunofluorescence assay demonstrated that there was no translocation of hTERT from nuclei to cytoplasm. Further studies revealed that the release of Ca(2+) was the underlying mechanism of suppressed TA and hTERT transcription in A549 cells exposed to HTMC. These in vitro data support the development of HTMC as a therapeutic agent for cancer complications.
Canadian Institute of Food Science and Technology journal, Oct 1, 1988
Abstract Previously reported rapeseed protein isolation methods resulted in low yields or low pro... more Abstract Previously reported rapeseed protein isolation methods resulted in low yields or low protein purity. The isolates often had an unpleasant taste or dark colour, and the levels of glucosinolates, phytates or both in these products were a source of concern. A novel processing scheme was developed which included extraction with an aqueous sodium hexametaphosphate or sodium hydroxide solution, ultrafiltration, isoelectric precipitation at pH 3.5, and diafiltration. An isoelectric protein fraction and a soluble protein fraction were produced. Up to 71.2% of the nitrogen was recovered in the isolates. The protein content of the isoelectric protein and soluble protein isolate was close to or higher than 90% (N × 6.25). A phy-tate content of less than 2% was achieved. These isolates were free of glucosinolates.
Response surface methodology (RSM) was employed to study the effect of culture medium on the prod... more Response surface methodology (RSM) was employed to study the effect of culture medium on the production of lovastatin in mixed solid-liquid state (or submerged) cultures by Monascus ruber. The maximal lovastatin yield (131 mg/L, average of three repeats) appeared at the region where the respective concentrations of rice powder, peptone, glycerin, and glucose were around 34.4 g/L, 10.8 g/L, 26.4 ml/L, and 129.2 g/L, respectively. The optimized medium resulted in a significant increase of lovastatin yield, as compared with that obtained by the fermentation of many other M. ruber species.
Applied Biochemistry and Biotechnology, Mar 8, 2022
4-Acetylantroquinonol B (4-AAQB) was identified in the rare fungus Antrodia cinnamomea and has be... more 4-Acetylantroquinonol B (4-AAQB) was identified in the rare fungus Antrodia cinnamomea and has been proven to be a potential therapeutic agent for cancer treatment. But the extraction of 4-AAQB from the fruit body led to a low yield and limited its further application in the pharmaceutical field. In this work, 4-AAQB production was enhanced in the submerged fermentation by the combination of exogenous additives, surfactants with the in situ extractive fermentation. 4-Methylbenzoic acid was proven to be an efficient additive for the accumulation of 4-AAQB by Antrodia cinnamomea, while 2% (w/v) Tween-80 added on the first day as surfactant and 30% (w/v) oleic acid added on the sixteenth day as extractant were the most available couples for 4-AAQB production in the in situ extractive fermentation. The combination of these multiple strategies resulted in the yield of 4-AAQB to 17.27 mg/g dry cell weight with a titer of 140 mg/L, which was the highest titer of 4-AAQB reported so far. It showed that the combination of these strategies had a significant promotion on 4-AAQB production by A. cinnamomea, which laid a good foundation for its large-scale production and also provided a viable method for the cultivation of other rare fungi.
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