Review Article

Traditional Uses, Bioactive Constituents, Biological Functions, and Safety Properties of Oviductus ranae as Functional Foods in China

Table 2

Biological functions of Oviductus ranae and its active principles.

Healthy functionsActive principle/preparationModelDosageResultsReference

Immunomodulatory activitiesOviductus ranaeMice (in vivo)0.67 and 1.33 g/kg BW, i.g., for 30 daysEnhance lymphocyte proliferation, antibody-producing cells, delayed-type hypersensitivity response, NK cell activity, and phagocytosis of mononuclear macrophages[73]
Oviductus ranae protein hydrolysate prepared by neutral proteaseSplenic lymphocyte and RAW 264.7 cells (in vitro)500 μg/mLIncrease spleen lymphocyte proliferation, IL-2 production, macrophage phagocytosis, and NO production[74]
Oviductus ranae protein hydrolysates prepared by different proteasesRAW 264.7 cells (in vitro)500 μg/mLImprove macrophage phagocytosis and NO production[75]
Oviductus ranae protein hydrolysate prepared by trypsinSplenic lymphocyte and RAW 264.7 cells (in vitro)50-800 μg/mLIncrease spleen lymphocyte proliferation, macrophage phagocytosis, and NO production[76]
Oviductus ranae protein hydrolysates prepared by different proteasesRAW 264.7 cells (in vitro)10-2000 μg/mLEnhance macrophage phagocytosis and productions of IL-1β, IL-6, TNF-α, NF-κB, and NO; upregulate the mRNA and protein expression of iNOS[77]
Peptide from Oviductus ranaeSplenic lymphocyte (in vitro)
Mice (in vivo)
20-100 mg/mL (in vitro); 600 mg/kg BW, i.g., for 30 days (in vivo)Increase spleen lymphocyte proliferation and immune organ index[78]
Compound Renshen-Hamayou capsuleMice (in vivo)1.5 g/kg BW, i.g., for 45 daysEnhance delayed-type hypersensitivity response and spleen lymphocyte proliferation[79]
Hamayou soft capsuleHealthy male athletes aged from 18 to 24 years (in vivo)Three times a day, 4 g each time, P.O., for 28 daysIncrease CD3+, CD4+, and CD4+/CD8+ ratio[80]
Antioxidant activitiesOviductus ranaeMice exposed to cold stress (in vivo)0.5 and 2.5 g/kg BW, i.g., for 28 daysIncrease SOD; decrease MDA[81]
Oviductus ranaeYoung and aging mice (in vivo)0.45, 1.35, and 2.25 g/kg BW, i.g., for 15, 30, and 45 days, respectivelyUpregulate the expression of Cu/Zn-SOD and GPx4 genes[82]
Serum from Oviductus ranae-treated ratsH2O2-induced oxidative stress in rat ovarian granulosa cells (in vitro)0.09, 0.27, and 0.81 g/kg BW, i.g., for 7 daysDecrease apoptosis by reducing ROS production and improving mitochondrial membrane potential through downregulating p53, Bax, caspase-3, and caspase-9 and upregulating Bcl-2; weaken phosphorylation of JNK and p38 MAPK; enhance ERK1/2 phosphorylation[83]
Water-soluble proteins from Oviductus ranaeHydroxyl, DPPH, and superoxide anion radicals and reducing power (in vitro)1-5 mg/mL; 2-10 mg/mL; 8-16 mg/mLWeak radical-scavenging capacities towards hydroxyl, DPPH, and superoxide anion as well as reducing power to ferric iron[84]
Ethanol-induced oxidative stress in mice (in vivo)0.1, 0.2, and 0.4 g/kg BW, i.g., for 30 daysIncrease T-SOD and GSH; decrease MDA and PCO
Four proteins from Oviductus ranaeDPPH and hydroxyl radicals and phosphatidylcholine liposome (in vitro)0.01-10 mg/mLWater-soluble and salt-soluble proteins possess stronger in vitro antioxidant capacities than gliadin and alkali-soluble protein.[85]
Two polypeptides from Oviductus ranae proteinDPPH, hydroxyl, and superoxide anion radicals (in vitro)2-12 mg/mLPolypeptide with molecular weight of 1~5 kDa exerts stronger in vitro antioxidant activity than the polypeptide with molecular weight of 5~8 kDa.[86]
Oviductus ranae/water-soluble proteins and water-insoluble constituents from Oviductus ranae/three hydrolysates from Oviductus ranae water-soluble proteinDPPH, hydroxyl, and superoxide anion radicals (in vitro)2-10 mg/mLWater-soluble proteins display stronger in vitro antioxidant capacity than Oviductus ranae and water-insoluble constituents. After hydrolysis, the activity was increased and protein hydrolysates prepared by neutral protease show the highest activity.[87]
Compound Renshen-Hamayou capsuleAging rats (in vivo)1.25 g/kg BW, i.g., for 60 daysDecrease MDA; increase GSH-Px activity[88]
Compound Linwayou granuleX-ray-induced oxidative stress in mice (in vivo)100 and 200 mg/kg BW, i.g., for 7 daysIncrease SOD and GSH-Px activities[89]
Antifatigue activitiesOviductus ranaeMice (in vivo)0.25, 0.5, and 1.0 g/kg BW, i.g., for 30 daysProlong the endurance time of FST, increase liver glycogen, and decrease BLA[90]
Oviductus ranae and its extractsHydrocortisone-induced kidney Yang deficiency syndrome in mice (in vivo)OR: 680 mg/kg BW; PEEOR: 136 mg/kg BW for 7 daysOR and PEEOR can increase body temperature and body weight and prolong the endurance time of rotarod test, hypoxia tolerance test, and FST.[91]
Oviductus ranaeHigh-intensity exercise training rats (in vivo)0.5, 1.0, and 3.0 g/kg BW, i.g., for 6 weeksIncrease body weight, endurance time of FST, testosterone, hemoglobin, and hepatic and muscle glycogen; decrease BUN[92]
Water-soluble proteins from Oviductus ranaeMice (in vivo)0.075, 0.15, and 0.3 g/kg BW, i.g., for 30 daysIncrease hepatic glycogen; decrease BLA[93]
Protein hydrolysates from Oviductus ranaeMice (in vivo)0.052, 0.52, and 1.56 g/kg BW, i.g., for 30 daysIncrease the endurance time of FST; decrease BUN and BLA[94]
Peptides from Oviductus ranaeMice (in vivo)100, 200, and 400 mg/kg BW, i.g., for 30 daysProlong the endurance time of FST, rotarod test, and pole-jumping test; reduce BUN and BLA[95]
Water-insoluble components from Oviductus ranaeMice (in vivo)0.25, 0.5, and 1.0 g/kg BW, i.g., for 30 daysIncrease the endurance time of FST and hepatic glycogen; decrease BLA[96]
Linwayou soft capsuleMice (in vivo)1.0, 2.0, and 3.0 g/kg BW, i.g., for 30 daysIncrease the endurance time of FST and hepatic glycogen; decrease BLA and BUN[97, 98]
Compound Linwayou-Yuhuangmo capsuleMice (in vivo)0.7, 1.4, and 2.1 g/kg BW, i.g., for 30 daysIncrease the endurance time of FST and hepatic glycogen; decrease BLA and BUN[99]
Antiaging activitiesOviductus ranaeDrosophila melanogaster (in vivo)0.34 and 0.68 mg/g culture mediumIncrease life-span, resistance to cold, and lipofuscin[100]
Oviductus ranaeD-Galactose-induced aging mice (in vivo)0.1, 0.2, and 0.4 g/kg BW, i.g., for 43 daysDecrease MDA and XOD; increase MPO and NO[101]
Oviductus ranaeD-Galactose-induced aging rats (in vivo)0.45, 0.9, and 1.8 g/kg BW, i.g., for 28 daysUpregulate the expressions of cyclin D1, CDK6, and p15; downregulate p16 and p21[102105]
Water-soluble proteins from Oviductus ranaeD-Galactose-induced aging mice (in vivo)0.075, 0.15, and 0.30 g/kg BW, i.g., for 30 daysDecrease MDA; increase SOD[106]
Water-insoluble constituents from Oviductus ranae and their hydrolysatesD-Galactose-induced aging mice (in vivo)0.15 and 0.3 g/kg BW, i.g., for 30 daysWater-insoluble constituents from Oviductus ranae can reduce MDA. Hydrolysates can decrease MDA and increase SOD and GSH-Px.[107]
Hamayou capsuleD-Galactose-induced aging mice (in vivo)1.4 and 2.8 g/kg BW, i.g., for 28 daysAlleviate pathological changes of ovary and uterus; increase SOD, organ indexes of ovarian and uterine, estradiol and estrous cycle; decrease MDA[108]
Estrogen-like activitiesSerum from Oviductus ranae-treated ratsRat ovarian granulosa cells (in vitro)4.5 g/kg BW, i.g., for 5 daysIncrease proliferation and E2 secretion, inhibit apoptosis, and protect ovarian granulosa cells[109]
Oviductus ranaeMice (in vivo)0.05 and 0.2 g/kg BW, i.g., for 37 daysIncrease E2, FSH, T, and P; increase the thickness of uterine wall and the number of corpora atretica; enhance the expression of FSHR gene[110]
Compound Rhizoma curcumae-Oviductus ranaeOvariectomized rats (in vivo)0.5, 1.0, and 2.0 g/kg BW, i.g., for 12 weeksIncrease E2, T, P, and IL-2; decrease FSH and LH; enhance the expression of ER[111]
Hepatoprotective activitiesOviductus ranaeCCl4-induced liver fibrotic rats (in vivo)1.5 and 3.0 g/kg BW, i.g., for 8 weeksDecrease ALT, AST, ALP, GGT, Hyp, and MDA; increase SOD and GSH-Px[112]
Oviductus ranaeEthanol-induced liver fibrotic rats (in vivo)3 g/kg BW, i.g., for 8 weeksIncrease glycogen granule; hepatocyte nuclear appeared to be large and round.[113]
Oviductus ranaeHigh-intensity exercise training mice (in vivo)0.9, 4.5, and 9.0 g/kg BW, i.g., for 28 daysDecrease MDA in the liver, increase SOD in the liver, and improve the ultrastructure of impaired hepatic cells[114]
Hypolipidemic activitiesOviductus ranaeHigh-fat-diet-induced hyperlipidemic rats (in vivo)0.05, 0.1, and 0.2 g/kg BW, i.g., for 30 daysDecrease TC and TG[115]
Water-insoluble constituents and their hydrolysates from Oviductus ranaeHigh-fat-diet-induced hyperlipidemic rats (in vivo)0.05, 0.1, and 0.2 g/kg BW, i.g., for 30 daysDecrease TC and TG; the effects of hydrolysates were superior to water-insoluble constituents.[116, 117]
Water-soluble proteins from Oviductus ranaeHigh-fat-diet-induced fatty rats (in vivo)0.05, 0.1, and 0.2 g/kg BW, i.g., for 30 daysDecrease TC and TG[118]
Antiosteoporotic activitiesOviductus ranaeOvariectomized rats (in vivo)0.05 g/kg BW, i.g., for 12 weeksIncrease calcium, estrogen, BMD, bone scan index, femoral weight, W.th, and osteocalcin; decrease ALP, phosphorus, and BGP; enhance the proliferation of osteoblastic cells and the formation of mineralized nodes; reduce the number of TRAP-positive cells[119]
Oviductus ranaeWomen with postmenopausal osteoporosis (in vivo)1 g per day, P.O., for 6 monthsImprove clinical signs and symptoms; increase E2; decrease BALP, IL-6, and BGP[120]
Antidepressant activitiesPetroleum ether extract of Oviductus ranaeBehavioral despair model of depression in mice (in vivo)
Antagonism of reserpine-induced hypothermia in mice (in vivo)
100, 300, and 900 mg/kg BW, i.g., for 8 daysDecrease the dead time of FST and TST, CORT, and akinesia; increase body temperature[121]
Petroleum ether extract of Oviductus ranaeChronic mild stress model of depression in rats (in vivo)30, 100, and 300 mg/kg BW, i.g., for 21 daysIncrease body weight, motion distance of OFT, and sucrose preference; decrease CORT; upregulate the expression of BDNF protein[122]
1-MethylhydantoinChronic forced swim stress-induced depression in rats (in vivo)20, 40, and 80 mg/kg BW, i.g., for 14 daysIncrease body weight and sucrose preference; decrease CORT; upregulate the expression of BDNF protein[123]
Antitussive, expectorant, antiasthmatic, and anti-inflammatory activitiesOviductus ranae and its different extractsSulfur dioxide and ammonia-induced cough in mice (in vivo)OR: 680 mg/kg BW; PEEOR: 68 and 136 mg/kg BW; MEOR: 85 and 170 mg/kg BW, i.g., for 3 and 7 days, respectivelyProlong the incubation period of cough and reduce cough frequency (efficiency: ); increase phenol red expectoration (efficiency: ) and sputum ejection (efficiency: )[124]
Oviductus ranaeOvalbumin-induced allergic asthma in mice (in vivo)0.05 and 0.5 g/kg BW, i.g., for 8 weeksDecrease inflammatory cell count, IL-4, IL-5, and IFN-γ in BALF[125]
1-MethylhydantoinOvalbumin-induced allergic asthma in rats (in vivo)40 and 80 mg/kg BW, i.g., for 7 daysDecrease IL-5, eotaxin, and eosinophil count in BALF[126]
Acetylcholine-induced bronchial asthma in guinea pigs (in vivo)30 and 60 mg/kg BW, i.g., for 3 daysProlong the incubation period of asthma
Histamine-induced contraction of guinea pig tracheal smooth muscle (in vitro)0.5 and 1.0 g/LIncrease antispasmodic percentage
Ammonia-induced cough in mice (in vivo)50 and 100 mg/kg BW, i.g., for 3 daysProlong the incubation period of cough and reduce cough frequency
Citric acid-induced cough in guinea pigs (in vivo)30 and 60 mg/g BW, i.g., for 3 daysProlong the incubation period of cough and reduce cough frequency
Anticancer activitiesProtein hydrolysates from Oviductus ranaeHuman glioma C6 cell (in vitro)500 μg/mLInhibit glioma cell proliferation and colony formation; promote apoptosis in glioma cell; downregulate Bcl-2; upregulate Bax and cleaved caspase-3[127]
Glioma model in nude mice (in vivo)1.5 g/kg BW, i.g.Inhibit glioma growth; increase IL-1β, IL-6, and TNF-α; upregulate p-PI3K, AKT, and p-AKT

Abbreviations: BW: body weight; i.g.: intragastric administration; CD: cluster of differentiation; IL-2: interleukin-2; NK: natural killer; NO: nitric oxide; IL-1β: interleukin-1β; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; NF-κB: nuclear factor-κB; mRNA: messenger ribonucleic acid; iNOS: inducible nitric oxide synthase; P.O.: oral administration; T-SOD: total superoxide dismutase; SOD: superoxide dismutase; MDA: malondialdehyde; PCO; GPx4: glutathione peroxidase 4; ROS: reactive oxygen species; MAPK: mitogen-activated protein kinases; DPPH: 1,1-diphenyl-2-picrylhydrazyl; GSH: glutathione; GSH-Px: glutathione peroxidase; FST: forced swimming test; BUN: blood urea nitrogen; BLA: blood lactic acid; H2O2: hydrogen peroxide; XOD: xanthine oxidase; MPO: myeloperoxidase; CDK-6: cyclin-dependent kinases-6; E2: estradiol; FSH: follicle-stimulating hormone; T: testosterone; P: progesterone; FSHR: follicle-stimulating hormone receptor; TβRI: type I transform growth factor β receptor; TβRII: type II transform growth factor β receptor; LH: luteinizing hormone; ER: estrogen receptor; ALT: alanine aminotransferase; AST: glutamic-oxalacetic transaminase; ALP: alkaline phosphatase; GGT, γ-glutamyltransferase; Hyp: hydroxyproline; CCl4: carbon tetrachloride; TC: total cholesterol; TG: triglyceride; BGP: bone gla protein; BMD: bone mineral densities; W.th: wall thickness; TRAP: tartrate-resistant acid phosphatase; BALP: bone alkaline phosphatase; IL-6: interleukin-6; Runx2: runt-related transcription factor 2; BMP2: bone morphogenetic protein 2; TST: tail suspension test; CORT: corticosterone; OFT: open field test; BDNF: brain-derived neurotrophic factor; PEEOR: petroleum ether extract from Oviductus ranae; MEOR: methanol extract from Oviductus ranae; IL-4: interleukin-4; IL-5: interleukin-5; IFN-γ: interferon-γ; BALF: bronchial alveolus lavage fluid; IL-1β: interleukin-1β.