Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium
Abstract
:1. Introduction
2. The Pharmacological Activities of Major Epimedium Flavonoids
2.1. Icariin and Its Pharmaceutical Effects
2.2. Baohuoside I and Its Pharmaceutical Effects
2.3. Icaritin and Its Pharmaceutical Effects
2.4. Epimedin C and Its Pharmaceutical Effects
2.5. Other Flavonoids and Their Pharmaceutical Effects
3. The Biosynthetic Pathway of Prenylated Flavonoids in EF
4. Extraction Methods of Epimedium Flavonoids
4.1. Hot Water Extraction
4.2. Alcohol Extraction
4.3. Other Extraction Methods
5. Biotransformation and Biosynthesis of Epimedium Flavonoids
5.1. Biotransformation of Epimedium Flavonoids by Enzymes
Enzyme Type | Enzyme Name | Enzyme Source | Enzyme Characterization | Enzyme Functions | References |
---|---|---|---|---|---|
Rhamnosyl hydrolase | α-l-rhamnosidase (AmRha) | Aspergillus mulundensis | 107.27 kDa, glycoside hydrolase (GH) 78 family; the optimal activity was achieved at 65 °C and pH 5.5, wide application temperature range, high level of enzyme catalytic ability and stability in the range of pH 5.0–7.5, acting on α-1,2-rhamnoside and α-1,6-rhamnoside bonds directly connected with glucose. | Catalyzes the bioconversion of epimedin C to icariin | [112] |
α-l-rhamnosidase | Papiliotrema laurentii ZJU-L07 | 100 kDa; the optimal activity was achieved at 55° C and pH 7.0, sensitive to temperature, stable at a pH range of 5.5–9.0 with an activity of over 80%, higher selectivity to cleave the α-1,2 glycosidic linkage between glucoside and rhamnoside and the α-1,2 glycosidic linkage between rhamnoside and rhamnoside. | Produces icariin from epimedin C | [118] | |
α-l-rhamnosidase (PodoRha) | Paenibacillus odorifer | The molecular weight of the monomer was 100.12 kDa, the native recombinant PodoRha was a trimer, GH78 family; the optimal activity was achieved at 45 °C and pH 6.5, a broad range of activity within a pH range of 5.0–8.5, excellent thermostability at 40 °C and 35 °C, high specificity on α-1,2-glycoside in epimedin C. | Converts epimedin C into icariin | [114] | |
α-l-rhamnosidase (DthRha) | Dictyoglomus thermophilum DSM3960 | 106.96 kDa, GH78 family; the optimal activity was achieved at 95 °C and pH 6.5, stable within the pH range of 4.5–7.5, residual activities exceeded 50% after incubation at 85 °C for 3 h and exceeded 90% after incubation at 75 °C for 3 h. Efficient hydrolyzation of the α-l-rhamnosidic bond of Epimedium flavonoids. | Converts epimedin C into icariin, converts icariin into icariside I, and converts baohuoside I into icaritin | [50] | |
α-l-rhamnosidase (synAnRhaE) | Aspergillus nidulans | 95 kDa; the optimal activity was achieved at 55 °C and pH 4.5, stable in an acidulous pH range below 55 °C, high specificity on α-1,2 rhamnoside glycosidic bond in epimedin C. | Converts epimedin C into icariin | [119] | |
α-l-rhamnosidase (SPRHA2) | Novosphingobium sp. GX9 | 120 kDa, GH106 family, when combined with PBGL, the optimal temperature for the reaction was 55 °C, and the highest activity was observed in 200 mM borate saline buffer at pH 8.5. | Catalyzes icariin into icariside I, converts baohuoside I into icaritin | [14] | |
α-l-rhamnosidase (BtRha) | Bacteroides thetaiotaomicron VPI-5482 | 83.3 kDa, GH78 family; the optimal activity was achieved at 55 °C and pH 6.5, high selectivity to cleave the α-1,2 and α-1,6 glycosidic bond between rhamnoside and rhamnoside, rhamnoside and glycoside, respectively. | Transforms epimedin C to icariin | [120] | |
α-l-rhamnosidase (Rhase-I) | Talaromyces stollii CLY-6 | 140 kDa, GH106 family; the optimal activity was achieved at 45 °C and pH 4.5, high thermal stability at a temperature lower than 50 °C and superior stability in an acidic environment (pH 2.0–5.0), be activated by Ca2+ and Mg2+, efficiently cleaving both the outer and inner rhamnosidic bonds of epimedin C. | Converts epimedin C into icariin, and converts icariin into icariside I | [121] | |
α-l-rhamnosidase (AtRha) | Aspergillus terreus CCF3059 | 96.9 kDa, GH78 family; the optimal activity was achieved at 60 °C and pH 6.5, excellent thermal stability and pH stability, hydrolyzed icariin containing the α-1 rhamnoside linkage. | Hydrolyzes icariin to icariside I | [122] | |
Glucosyl hydrolase | β-glucosidase (Tpebgl3) | Thermomotoga petrophila DSM 13,995 | 81.24 kDa, GH3 family; the optimal activity was achieved at 90 °C and pH 5.0, the thermostability of the enzyme was improved by Ca2+, good stability at high temperatures and organic solvents. | Produces baohuoside I from icariin | [31,123] |
β-glucosidase (IagBgl1) | Ignisphaera aggregans | The molecular weight of the monomer was 56.36 kDa, the native recombinant IagBgl1 was a trimer, GH1 family; the optimal activity was achieved at 95 °C and pH 6.5, thermostable and glucose-tolerant, retained more than 70% after incubation at 90 °C for 4 h, high catalytic activity towards icariin. | Produces baohuoside I from icariin | [32] | |
β-glucosidase (PBGL) | Paenibacillus cookii GX-4 | 84 kDa, GH3 family, when combined with SPRHA2, the optimal temperature for the reaction was 55 °C, and the highest activity was observed in 200 mM borate saline buffer at pH 8.5. | Converts icariin into baohuoside I, converts icariside I to icaritin | [14] | |
β-1,3-glucanase (CtLam55) | Chaetomium thermophilum | 82.7 kDa, GH55 family; the optimal activity was achieved at 60 °C and pH 5.0, thermostable at 50 °C, exo-β-1,3-glucanase activity. | Hydrolyzes icariin to baohuoside I | [113,124] | |
β-glucosidase (Dth3) | Dictyoglomus thermophilum DSM3960 | 88.7 kDa, GH3 family; the optimal activity was achieved at 90 °C and pH 5.5, highly tolerant to glucose. | Converts epimedin A into baohuoside I, converts icariin into baohuoside I | [112,115] | |
β-glucosidase | Trichoderma viride | 60 kDa; the optimal activity was achieved at 41 °C and pH 4.0. | Prepares baohuoside I from icariin | [125] | |
dextranase | - | The optimal activity was achieved at 40 °C and pH 5.4, sensitive to pH. | Hydrolyzes icariin to baohuoside I | [126] | |
cellulase | - | The optimum conditions for the cellulase were 50 °C and pH 5.0. | Transforms icariin to baohuoside I | [127] | |
Xylosyl hydrolase | β-xylosidase (BbXyl) | Bifidobacterium breve K-110 | 70 kDa, GH43 family; the optimal activity was achieved at 45 °C and pH 5.5, the residual activity was more than 80% after being incubated at 45 °C for 4 h, showed over 70% of the maximum activity at a pH from 4.5 to 7.0, higher catalytic efficiency and selection specificity. | Converts epimedin B into icariin | [128] |
β-xylosidase (Dt-2286) | Dictyoglomus turgidum | 85.1 kDa, GH3 family; the optimal activity was achieved at 98 °C and pH 5.0, excellent thermostable/haloduric/organic solvent-tolerance, a multifunctional enzyme with β-xylosidase, α-arabinofuranoside, α-arabinopyranoside and β-glucosidase activities. | Converts epimedin B into sagittatoside B, and converts sagittatoside B into icariside I | [129] | |
β-xylosidase (Dth3) | Dictyoglomus thermophilum DSM3960 | 88.7 kDa, GH3 family; the optimal activity was achieved at 90 °C and pH 5.5, activity was not affected by xylose in high concentration. | Converts epimedin B into baohuoside I | [112,115] |
5.2. Biotransformation of Epimedium Flavonoids by Whole-Cell Catalysis
5.3. Complete Biosynthesis of Epimedium Flavonoids
6. Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Epimedium Flavonoids | Research Systems | Mechanisms | Reference |
---|---|---|---|
Alcohol extracts of E. koreanum Nakai and E. wushanense T.S. Ying | SD rats | Compared with the normal group, animal groups treated with EF extracts showed severer hepatotoxicity, which was positively correlated with the dose and course. Additionally, the females experienced more significant damage compared to the males. | [90] |
Icariside I and sagittatoside A | HL-7702 and HepG2 cells | Icariside I could destroy the cell structure and cause oxidative stress. Sagittatoside A could cause oxidative stress and damage to mitochondria. | [91] |
Epimedin C | Male Balb/c mice | Epigenetic modification changed in mouse liver after epimedin C treatment with a test dose, and the m6A and m5C may be associated with epimedin C-induced liver injury. | [92] |
Baohuoside I | HL-7702 and HepG2 cells | The toxicity mechanism(s) of baohuoside I may be involved in increasing oxidative stress and inducing apoptosis. | [93] |
E. koreanum Nakai ethanol extract | Male Sprague Dawley rats | The mechanism of hepatotoxicity of E. koreanum Nakai was probably related to the induction of ferroptosis in hepatocytes. | [94] |
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Zhang, X.; Tang, B.; Wen, S.; Wang, Y.; Pan, C.; Qu, L.; Yin, Y.; Wei, Y. Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium. Molecules 2023, 28, 7173. https://doi.org/10.3390/molecules28207173
Zhang X, Tang B, Wen S, Wang Y, Pan C, Qu L, Yin Y, Wei Y. Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium. Molecules. 2023; 28(20):7173. https://doi.org/10.3390/molecules28207173
Chicago/Turabian StyleZhang, Xiaoling, Bingling Tang, Sijie Wen, Yitong Wang, Chengxue Pan, Lingbo Qu, Yulong Yin, and Yongjun Wei. 2023. "Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium" Molecules 28, no. 20: 7173. https://doi.org/10.3390/molecules28207173