RESUMEN
Muscle atrophy caused by an imbalance between the synthesis and the degradation of proteins is a syndrome commonly found in the elders. Teaghrelin, a natural compound from oolong tea, has been shown to promote cell differentiation and to inhibit dexamethasone-induced muscle atrophy in C2C12 cells. In this study, the therapeutic effects of teaghrelin on muscle atrophy were evaluated in Sprague Dawley rats treated with dexamethasone. The masses of the soleus, gastrocnemius and extensor digitorum longus muscles were reduced in dexamethasone-treated rats, and the reduction of these muscle masses was significantly attenuated when the rats were supplemented with teaghrelin. Accordingly, the level of serum creatine kinase, a marker enzyme of muscle proteolysis, was elevated in dexamethasone-treated rats, and the elevation was substantially reduced by teaghrelin supplementation. A decrease in Akt phosphorylation causing the activation of the ubiquitin-proteasome system and autophagy for protein degradation was detected in the gastrocnemius muscles of the dexamethasone-treated rats, and this signaling pathway for protein degradation was significantly inhibited by teaghrelin supplementation. Protein synthesis via the mTOR/p70S6K pathway was slowed down in the gastrocnemius muscles of the dexamethasone-treated rats and was significantly rescued after teaghrelin supplementation. Teaghrelin seemed to prevent muscle atrophy by reducing protein degradation and enhancing protein synthesis via Akt phosphorylation.
Asunto(s)
Atrofia Muscular , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-akt/metabolismo , Atrofia Muscular/inducido químicamente , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Dexametasona/efectos adversos , Suplementos DietéticosRESUMEN
Obesity is closely linked with metabolic diseases, while life and prenatal exposure to endocrine-disrupting chemicals has been implicated in the development of obesity. Magnesium lithospermate B (MLB), an active compound of Salvia miltiorrhiza (Danshen), has beneficial effects on insulin resistance and metabolic abnormalities in diet-induced obese rodents. Since exposure to endocrine-disrupting chemical Bisphenol A (BPA) during pregnancy mimics the effects of high fat diet-induced alterations of glucose and lipid metabolism in adult male offspring, the effects of daily MLB supplementation for 4 weeks on metabolic abnormalities in rats weaning from prenatal BPA-exposed dams were investigated. BPA-exposed rats developed obesity and adiposity concurrent with hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and elevation of circulating glucagon and free fatty acids. Increased hepatic fatty acid synthesis and decreased fatty acid ß-oxidation, activation of adipocytic adipogenesis, maturation, and lipogenesis, as well as reduction of muscular glucose uptake were demonstrated in BPA-exposed rats. The aforementioned alterations were improved by MLB supplementation. Additionally, MLB displayed negative effects on glucocorticoid receptor action and inflammation, and promoted lipolysis and thermogenesis in the adipose tissues. In conclusion, our findings suggest that MLB may be a potential therapeutic compound against metabolic diseases, including maternal exposure-induced metabolic abnormalities.
Asunto(s)
Compuestos de Bencidrilo , Efectos Tardíos de la Exposición Prenatal , Animales , Compuestos de Bencidrilo/toxicidad , Suplementos Dietéticos , Medicamentos Herbarios Chinos , Femenino , Masculino , Fenoles/toxicidad , Embarazo , RatasRESUMEN
Hyperglycemia is a well-known indicator of stroke prognosis, and one-third of nondiabetic patients develop postischemic hyperglycemia during the acute phase of stroke; this is related to relatively poor prognosis, high mortality, and impaired neurological recovery. Interleukin-13 (IL-13), a member of the Th2 cytokine family, is involved in both the regulation of immune response and glucose metabolism. Thus, we investigated the mechanism of postischemic hyperglycemia and the role of IL-13 by using a permanent middle cerebral artery occlusion (MCAO) rat model. Our results indicated that postischemic hyperglycemia was accompanied with hyperinsulinemia and increased HOMA-IR, elevated hepatic gluconeogenesis, and suppressed insulin signaling. A shift towards inflammatory response was evident with results of elevated proinflammatory cytokines and increased expression of negative regulatory proteins, suggesting an ongoing vicious cycle of inflammatory-induced insulin-resistant hyperglycemia. IL-13 treatment counteracted the proinflammatory states and abolished the vicious cycle through enhancing STAT6 and STAT3, which mediated the immune and metabolic pathways respectively; these effects resolved the formerly described pathological changes of postischemic hyperglycemia and reduced infarction size in the MCAO rats. Our findings demonstrated the importance of Th1-Th2 balance in the peripheral glucose metabolism affected by acute ischemic stroke, which provides a new perspective for the prevention and control of postischemic hyperglycemia.
Asunto(s)
Isquemia Encefálica/complicaciones , Gluconeogénesis/efectos de los fármacos , Hiperglucemia/tratamiento farmacológico , Interleucina-13/farmacología , Hígado/efectos de los fármacos , Animales , Glucemia/metabolismo , Isquemia Encefálica/metabolismo , Modelos Animales de Enfermedad , Hiperglucemia/etiología , Hiperglucemia/metabolismo , Resistencia a la Insulina/fisiología , Interleucina-13/uso terapéutico , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Excessive food consumption and insufficient exercise lead to the prevalence of metabolic syndrome in modern life, which consequently increases the risk of many chronic diseases. Magnesium lithospermate B (MLB) from Danshen has been demonstrated to improve metabolic changes in high-fat diet-fed rats with metabolic syndrome. In this study, Mg2+ in MLB was successfully replaced with Zn2+ to form zinc lithospermate B (ZLB) complex. MLB (10 mg/kg /day) and ZLB of various concentrations (1, 2.5, 5, and 10 mg/kg/day) were prepared and examined for their therapeutic effects on metabolic syndrome induced in rats fed with a high-fat diet. The results showed that both MLB and ZLB were able to recover or alleviate the abnormal physiological states of high-fat diet-fed rats including weight gain, epididymal fat accumulation, fatty liver, retarded blood lipid and glucose metabolism putatively caused by insulin resistance, and elevated levels of proinflammatory cytokine, leptin, and oxidative stress. In an overall view of the animal study, the effectiveness of ZLB supplementation seemed to be better than that of MLB supplementation for the recovery of high-fat-fed rats from metabolic syndrome.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Síndrome Metabólico/tratamiento farmacológico , Zinc/farmacología , Animales , Glucemia/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Medicamentos Herbarios Chinos/química , Humanos , Insulina/metabolismo , Leptina/sangre , Lípidos/sangre , Magnesio/química , Magnesio/farmacología , Síndrome Metabólico/etiología , Síndrome Metabólico/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Salvia miltiorrhiza , Aumento de Peso/efectos de los fármacos , Zinc/químicaRESUMEN
Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.
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Adiposidad/efectos de los fármacos , Antipsicóticos/efectos adversos , Cloruros/farmacología , Compuestos de Cromo/farmacología , Hiperglucemia/metabolismo , Hiperinsulinismo/metabolismo , Hiperlipidemias/metabolismo , Olanzapina/efectos adversos , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adiposidad/genética , Administración Oral , Animales , Cloruros/metabolismo , Compuestos de Cromo/metabolismo , Femenino , Regulación de la Expresión Génica , Hiperglucemia/inducido químicamente , Hiperglucemia/genética , Hiperglucemia/prevención & control , Hiperinsulinismo/inducido químicamente , Hiperinsulinismo/genética , Hiperinsulinismo/prevención & control , Hiperlipidemias/inducido químicamente , Hiperlipidemias/genética , Hiperlipidemias/prevención & control , Inflamación , Resistencia a la Insulina/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
The maturation of mastoparan B, the major toxin peptide in the venom of Vespa basalis, requires enzymatic cleavage of its prosequence presumably via sequential liberation of dipeptides. The putative processing enzyme, dipeptidyl peptidase IV, was expressed as a glycosylated His-tag fusion protein (rDPP-IV) via the baculovirus expression system. rDPP-IV purified by one-step nickel-affinity chromatography was verified by Western blot and LC-MS/MS analysis. The k(cat)/K(m) of rDPP-IV was determined to be in the range of 10-500 mM(-1)·S(-1) for five synthetic substrates. The optimal temperature and pH for rDPP-IV were determined to be 50 °C and pH 9. Enzymatic activity of rDPP-IV was significantly reduced by 80 and 60% in the presence of sitagliptin and phenylmethylsulfonyl fluoride respectively.
Asunto(s)
Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Avispas/enzimología , Avispas/genética , Secuencia de Aminoácidos , Animales , Baculoviridae/genética , Línea Celular , Cromatografía de Afinidad , Dipeptidil Peptidasa 4/química , Dipeptidil Peptidasa 4/aislamiento & purificación , Expresión Génica , Datos de Secuencia MolecularRESUMEN
The prevalence and incidence of Parkinson's disease (PD), an age-related neurodegenerative disease, are higher among elderly people. Independent of etiology, dysfunction and loss of dopaminergic neurons are common pathophysiological changes in PD patients with impaired motor and non-motor function. Currently, preventive or therapeutic treatment for combating PD is limited. The ghrelin axis and ghrelin receptor have been implicated in the preservation of dopaminergic neurons and have potential implications in PD treatment. Teaghrelin, a compound originating from Chin-Shin Oolong tea, exhibits ghrelin agonist activity. In this study, the neuroprotective potential of teaghrelin against PD was explored in a cell model in which human neuroblastoma SH-SY5Y cells were treated with the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+). Upon MPP+ exposure, SH-SY5Y cells exhibited decreased mitochondrial complex I activity and apoptotic cell death. Teaghrelin activated AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC-1α) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways to antagonize MPP+-induced cell death. Herein, we propose that teaghrelin is a potential candidate for the therapeutic treatment of PD.
Asunto(s)
1-Metil-4-fenilpiridinio/toxicidad , Adenilato Quinasa/metabolismo , Camellia sinensis/química , Supervivencia Celular/efectos de los fármacos , Ghrelina/agonistas , Sirtuina 1/metabolismo , Adenilato Quinasa/genética , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Sirtuina 1/genéticaRESUMEN
This study aimed to investigate the effects of teaghrelin, an active ingredient of Chin-shin oolong tea, on murine C2C12 myoblast cells. Under high serum conditions, teaghrelin inhibited C2C12â¯cell proliferation, indicating a cell cycle arrest and cessation of proliferative progression. Teaghrelin promoted pro-differentiation of C2C12â¯cells as evidenced by a progressively elongated morphology, as well as the induction of muscle specific myogenin, myosin heavy chain (MHC), and MyoD. The formation of multinucleated myotubes, and the increase of MHC-positive immunoreactivity within the myotubes, further reflected a complete differentiation and maturation of the contractile skeletal muscle cells induced by teaghrelin. Like ghrelin, teaghrelin attenuated dexamethasone-decreased myotube diameter, indicating its protective effects against skeletal muscle atrophy. Additionally, the expressions of Atrogin-1 and MuRF-1 ubiquitin E3 ligase were reduced. In conclusion, the results highlight a possibility of developing teaghrelin as a functional food for the prevention or therapeutic treatment of disease-associated skeletal muscle atrophy.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Ghrelina/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Atrofia Muscular/tratamiento farmacológico , Mioblastos/efectos de los fármacos , Extractos Vegetales/farmacología , Té/química , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Ratones , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Proteína MioD/metabolismo , Mioblastos/metabolismo , Miogenina/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Mastoparan B (MPB) is a venom peptide isolated from Vespa basalis (black-bellied hornet), one of the dangerous vespine wasps found in Taiwan. MPB is a tetradecapeptide (LKLKSIVSWAKKVL), amphiphilic venom peptide, with a molecular mass of 1.6 kDa. MPB belongs to an evolutionarily conserved component of the innate immune response against microbes. In this study, we attempted to modify a reliable oleosin-based fusion expression strategy coupled with the artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce bioactive MPB. OBJECTIVES: The aim of this study was to develop an artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce the bioactive form of mastoparan B (MPB), which in a manner identical to that of its native counterpart. METHODS: The plasmid pET30-His6-rOle(127MâL)-MPB was constructed, and then four different E. coli strains- BL21(DE3), BL21(DE3)pLysS, C41(DE3), and C43(DE3) were tested to identify the most suitable host for the pET30-His6-rOle(127MâL)-MPB fusion protein expression. We optimized the expression conditions by testing different growth temperatures, isopropyl-ß-D-thiogalactoside (IPTG) concentrations, and post-induction collection times. Afterwards, the His6-rOle(127MâL)-MPB protein was purified by one-step nickel-chelated affinity chromatography (Ni2+-NTA) under denaturing conditions. The purified His6-rOle(127MâL)-MPB was selectively cleaved by thrombin protease to remove the His6-tag and the leader peptide from the N-terminus. Subsequently, rOle(127MâL)-MPB protein was constituted into AOB and incubated with CNBr for a cleavage reaction, which resulted in the release of the MPB from rOle(127MâL)-MPB protein via AOB. The purified MPB was identified by MALDI-MS and HPLC analysis, and its bioactivity was examined by antimicrobial testing. RESULTS: After a 2-h induction period, the E. coli C43(DE3) was found to be superior to BL21(DE3) and the other protease-deficient strains as an expression host. And, the optimal His6-rOle(127MâL)-MPB expression at 37°C for 2 h after induction with 5 µM IPTG. The purified MPB showed that a single major peak was detected by HPLC/UV detection with a retention time of 22.5 minutes, which was approximately 90% pure. The putative MPB, and over two-third of the peptide sequence was verified by the MALDI-MS analysis. Finally, the purified MPB was examined by a broth dilution-antimicrobial susceptibility test. These results indicated that the purified MPB was bioactive and very effective in anti-bacterial (E. coli J96) activity. Here, we successfully used the oleosin-based fusion expression strategy coupled with the artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce bioactive MPB peptide which, in a manner identical to that of its native counterpart. CONCLUSION: In this study, the recombinant oleosin based fusion strategy coupled with AOB-CNBr purification platform open a new avenue for the production of active MPB and facilitate the studies and applications of the peptide in the future for medicinal applications such as hypotension and antibacterial effect.
Asunto(s)
Bromuro de Cianógeno/química , Gotas Lipídicas/química , Péptidos/química , Péptidos/genética , Ponzoñas/química , Secuencia de Aminoácidos , Antibacterianos/química , Antibacterianos/farmacología , Cromatografía Líquida de Alta Presión/métodos , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Escherichia coli , Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular , Isopropil Tiogalactósido/química , Tamaño de la Partícula , Péptidos/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/farmacologíaRESUMEN
Strictinin, the major phenolic compound in Pu'er teas produced from young leaves and buds of wild trees, was isolated to evaluate its antibacterial and laxative activities. The minimum inhibitory concentrations of strictinin against Propionibacterium acnes and Staphylococcus epidermidis were determined as 250 µM and 2000 µM, respectively, apparently higher than those of several antibiotics commonly used for bacterial infections. The additive and synergistic effects on the inhibitory activities of strictinin combined with other commercial antibiotics were observed in two bacteria tested in this study via the analysis of fractional inhibitory concentrations. Laxative activity was observed on defecation of the rats fed with strictinin. Further analysis showed that the laxative effect of strictinin was presumably caused by accelerating small intestinal transit, instead of enhancing gastric emptying, increasing food intake, or inducing diarrhea in the rats. Taken together with the antiviral activities demonstrated previously, it is suggested that strictinin is one of the active ingredients responsible for the antiviral, antibacterial, and laxative effects of wild Pu'er tea, and has the potential to be developed as a mild natural substitute for antibiotics and laxatives.
Asunto(s)
Camellia sinensis , Animales , Antibacterianos , Laxativos , Fenoles , Ratas , TéRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Folium Ginkgo, the dried leaf of Ginkgo biloba L. is a traditional Chinese medicine listed in the Pharmacopoeia of the People's Republic of China with several therapeutic effects, including prevention of aging. It is used as herbal medicine for the treatment of several aging-related diseases. The therapeutic effects of Folium Ginkgo on aging-related diseases are suspected to be similar to the anti-aging effects of growth hormone release induced by ghrelin. MATERIALS AND METHODS: Candidate components responsible for the anti-aging effects via the ghrelin receptor-activated pathway were searched from the known compounds found in Folium Ginkgo. Two acylated flavonoid diglycosides, tentatively named ginkgoghrelins in this study, were selected and isolated from the methanol extract of Folium Ginkgo, and their chemical structures were confirmed by spectroscopic analysis. These two compounds were examined for their capability of stimulating growth hormone release of rat primary anterior pituitary cells via activation of the ghrelin receptor. The major metabolites of ginkgoghrelins in rat bile were detected after intravenous injection and structurally analyzed by mass spectroscopy. Molecular modeling of ginkgoghrelins docking to the ghrelin receptor was exhibited to explore the possible interaction within the binding pocket. RESULTS: Similar to growth hormone-releasing hormone-6 (GHRP-6), a synthetic analog of ghrelin, ginkgoghrelins were demonstrated to stimulate growth hormone secretion of rat primary anterior pituitary cells in a dose dependent manner, and the stimulation was inhibited by [d-Arg1, d-Phe5, d-Trp7,9, Leu11]-substance P, an inverse agonist of the ghrelin receptor. Putative metabolites of ginkgoghrelins via glucuronidation and methylation were detected in bile of rats after intravenous injection. Molecular modeling and docking showed that ginkgoghrelins as well as GHRP-6 could fit in and adequately interact with the binding pocket of the ghrelin receptor. CONCLUSION: The results suggest that ginkgoghrelins are putative components partly accounting for the anti-aging effects of Folium Ginkgo possibly via activation of the ghrelin receptor, and possess great potential to be developed as non-peptidyl analogs of ghrelin.
Asunto(s)
Flavonoides/química , Ghrelina/farmacología , Glicósidos/química , Hormona del Crecimiento/metabolismo , Extractos Vegetales/química , Receptores de Ghrelina/metabolismo , Acilación , Animales , Ginkgo biloba , Masculino , Simulación del Acoplamiento Molecular , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Compared with abundant catechins, strictinin is a minor constituent in teas and has been demonstrated to possess inhibitory potency on influenza virus. In this study, strictinin was found as the major phenolic compound in Pu'er teas produced from leaves and buds of wild trees. Due to its thermal instability, strictinin, in tea infusion or in an isolated form, was completely decomposed to ellagic acid and gallic acid after being autoclaved for 7 minutes. A plaque reduction assay was employed to compare the relative inhibitory potency between strictinin and its thermally degraded products against human influenza virus A/Puerto Rico/8/34. The results showed that the antiviral activity of ellagic acid regardless of the presence or absence of gallic acid was significantly higher than that of strictinin. Thermal degradation of strictinin to ellagic acid and gallic acid seems to be beneficial for the preparation of Pu'er teas in terms of enhancing antiviral activity.
RESUMEN
Teaghrelins are unique acylated flavonoid tetraglycosides found in Chin-shin oolong tea, and have been demonstrated to be promising oral ghrelin analogues. The biosynthetic pathway of teaghrelins from quercetin-3-O-rutinoside (rutin) or kaempferol-3-O-rutinoside (nicotiflorin) was proposed to comprise three enzymatic steps according to the identification of putative intermediates in Chin-shin oolong tea. In addition to the two known teaghrelins in Chin-shin oolong tea, four teaghrelin-like compounds with different attachments of glycosides were identified in various oolong teas. Molecular modeling and docking were used to evaluate theoretically whether the putative biosynthetic intermediates of teaghrelins and the four teaghrelin-like compounds could be potential candidates of ghrelin analogues. The results showed that the attachment of a coumaroyl group was crucial for these tea compounds to bind to the ghrelin receptor. However, the additional attachment of a rhamnosyl glycoside to the flavonoid backbone of teaghrelin-like compounds at C-7 significantly reduced their binding affinity with the ghrelin receptor.
RESUMEN
Fip-gts, a fungal immunomodulatory protein (Fip) isolated from Ganoderma tsugae (gts), has been reported to possess therapeutic effects in the treatment of cancer and autoimmune disease. To cost-effectively produce Fip-gts and bypass the bottleneck involved in its time-consuming purification from G. tsugae, in this study, we incorporated the SP(bbx) secretion signal into recombinant baculovirus for expressing glycosylated and bioactive rFip-gts in baculovirus-infected insect cells and Trichoplusia ni larva. This is the first study to employ the aerosol infecting T. ni larva with recombinant baculovirus for economical and high-level production of foreign proteins. In this study, one purification could yield 10 mg of rFip-gts protein merely from â¼100 infected T. ni larvae by aerosol inoculation, corresponding to 5 L (5 × 109 cells) of the infected Sf21 culture. In addition, the rFip-gts purified from T. ni larvae could induce the expression of interleukin-2 in murine splenocytes with an immunoresponsive level similar to that induced by LZ-8 (a known potent immunomodulatory protein purified from Ling zhi, Ganoderma lucidum). Thus, our results demonstrated that the larva-based baculovirus expression system can successfully express rFip-gts with the assembling capability required for maintaining immunomodulatory and anticancer activity. Our approach will open a new avenue for the production of rFip-gts and facilitate the immunoregulatory activity of rFip-gts available in the future.