Preparation, characteristic, biological activities, and application of polysaccharide from Lilii Bulbus: a review.

OBJECTIVES: This review highlights the current knowledge of polysaccharide from Lilii Bulbus, including the extraction, purification, structure, structure modification, biological activities and application, which will hopefully provide reference for further research and development of polysaccharide from Lilii Bulbus. MATERIALS AND METHODS: Literature searches were conducted on the following databases: Pubmed, ACS website, Elsevier, Google Scholar, Web of Science and CNKI database. Keywords such as "Lilii Bulbus", "polysaccharide", "preparation", "biological activities" and "application" were used to search relevant journals and contents, and some irrelevant contents were excluded. RESULTS: In general, the study of Lilium Bulbus polysaccharide extraction and purification, structure characterization and biological activity has made substantial progress, these findings highlight the lilium brownii polysaccharide enormous potential in biomedical applications, of lilium brownii polysaccharide laid a solid foundation for further research. DISCUSSION AND CONCLUSIONS: However, it should be noted that the relevant mechanism of the effective effect of lily bulb polysaccharide still needs to be worked on by researchers. These findings highlight the great potential of lily polysaccharides in biomedical applications, and lay a solid foundation for further research on lily polysaccharides.

Mechanistic understanding of the improved drying characteristics and quality attributes of lily (Lilium lancifolium Thunb.) by modified microstructure after pulsed electric field (PEF) pretreatment.

The effects of the non-thermal (pulsed electric field, PEF) and thermal pretreatment (vacuum steam pulsed blanching, VSPB) on the drying kinetics, quality attributes, and multi-dimensional microstructure of lily scales were investigated. The results indicate that both PEF and VSPB pretreatments improved the drying rate compared to untreated lily scales. Specifically, PEF pretreatment reduced the drying time by 29.58 % - 43.60 %, while VSPB achieved a 46.91 % reduction in drying time. PEF treatment facilitated the enhanced leaching of phenols and flavonoids compared to VSPB treated samples, thereby increasing antioxidant activity. The rehydration ratio of the dried lilies was improved with PEF and VSPB treatment, which closely related to the microstructure. Weibull distribution and Page model demonstrated excellent fit for the drying and rehydration kinetics of lily scales, respectively (R2 > 0.993). The analysis of multi-dimensional microstructure and ultrastructure confirmed the variations in moisture migration and phytochemical contents among different treatments. Consequently, this study offers insights into the technological support for the potential of non-thermal pretreatment in fruits and vegetables.

Two New Phenylpropanoid Compounds from Lilium Brownii and Their Anti-monoamine Oxidase Activity.

Baihe is a commonly used Chinese medicine for the treatment of neurological disorders. Clinically, the bulbs of Lilium brownii are used to act as Baihe. In the study, two new phenylpropanoid compounds including 3-O-acetyl-1-O-caffeoylglycerol (1) and 3-O-acetyl-1-O-p-coumaroylglycerol (2) were isolated from the bulbs of L. brownii. Their structures were identified by spectroscopic method and the effect on monoamine oxidase activity was determined using an enzyme labeling method. The results show 1 and 2 have anti-monoamine oxidase activity with 20.96 % and 22.31 % inhibition rates at 50 µg/ml, respectively.

Extraction, purification, structural characteristics, biological activities, and applications of polysaccharides from the genus Lilium: A review.

The genus Lilium (Lilium) has been widely used in East Asia for over 2000 years due to its rich nutritional and medicinal value, serving as both food and medicinal ingredient. Polysaccharides, as one of the most important bioactive components in Lilium, offer various health benefits. Recently, polysaccharides from Lilium plants have garnered significant attention from researchers due to their diverse biological properties including immunomodulatory, anti-oxidant, anti-diabetic, anti-tumor, anti-bacterial, anti-aging and anti-radiation effects. However, the limited comprehensive understanding of polysaccharides from Lilium plants has hindered their development and utilization. This review focuses on the extraction, purification, structural characteristics, biological activities, structure-activity relationships, applications, and relevant bibliometrics of polysaccharides from Lilium plants. Additionally, it delves into the potential development and future research directions. The aim of this article is to provide a comprehensive understanding of polysaccharides from Lilium plants and to serve as a basis for further research and development as therapeutic agents and multifunctional biomaterials.

Two New Isospirostanol-Type Saponins from the Bulbs of Lilium Brownii and Their Anti-Hepatocarcinogenic Activity.

Bulbs of Lilium brownii, commonly known as "Bai-he" in China, serve both edible and medicinal purposes in clinical practice. In this study, two new isospirostanol-type saponins were isolated from L. brownii, and their structures were identified by spectroscopic method, and absolute configurations were elucidated by comprehensive analysis of spectral data obtained from combined acid hydrolysis. Two compounds were finally identified as 3-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside]-(22R,25R)-5α-spirosolane-3ß-ol (1) and 3-O-{α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside}-(22R,25R)-5α-spirosolane-3ß-ol (2), respectively. Further, we found that compound 2 significantly suppressed the proliferation of SMMC-7721 and HepG2 cells with IC50 values of 26.3±1.08 µM and 30.9±1.59 µM, whereas compound 1 didn't inhibit both of the two hepatocellular carcinoma. Subsequently, compound 2 effectively decreased the levels of interleukin-1ß and tumor necrosis factor-α and the expression of Bcl-2, and increased the expression of Bax and Caspase-3 proteins. Which indicated that the anti-hepatocellular carcinoma effect of compound 2 involves reducing the level of inflammation and inducing apoptosis.

Extraction, structural characterization and immunoactivity of glucomannan type polysaccahrides from Lilium brownii var. viridulum Baker.

Homogeneous polysaccharide (LBP) was extracted and purified from the bulblets of Lilium brownii var. viridulum Baker with a molecular weight of 312 kDa. The monosaccharides are composed of mannose and glucose, and the corresponding molar ratios are 0.582 and 0.418, respectively. FT-IR, LC-MS, NMR, GC-MS and HPAEC were used to analyze the functional groups, glycosidic linkages and chemical structure of LBP, which was a 1-4-linked glucomannan and contained a dodecasaccharide repeating units of →4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-α-D-Glcp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ . In vitro experimental results showed that LBP had noble biocompatibility, and a low dose of 5 µg/mL LBP significantly up-regulated the mRNA expression of TNF-α, iNOS, IL-6, IL-1ß and Toll-like receptors family (TLRs) in RAW 264.7 cells. In conclusion, LBP played an important role in immunomodulation, and further studies on the specific immunomodulatory mechanisms of LBP on RAW 264.7 cells are still needed.

Four new steroidal glycosides from Lilium lancifolium Thunb. and their antitumor activity.

Four new steroidal glycosides (1-4), including two steroidal saponins named lililancifoloside B and C (1-2), one pregnane glycoside named lililancifoloside D (3), and one C22-steroidal lactone glycoside named lililancifoloside E (4), together with five known ones (5-9), were isolated from the bulbs of Lilium lancifolium Thunb. By using spectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS, the structures of 1-4 were elucidated. All isolates were tested for their cytotoxic potential against the MCF-7, MDA-MB-231, HepG2, and A549 cell lines. Compound 6 distinguished out among them, IC50 values of 3.31, 5.23, 1.78, and 1.49 µM against the four cell lines, respectively. Other compounds such as compound 3, 5, and 9 have also shown specific cytotoxic activity. Next, studies showed that compound 6 might cause HepG2 cells to undergo a cell cycle arrest during the G2/M phase and apoptosis.

Extraction, structure, pharmacological activity, and structural modification of Lilium polysaccharides.

Polysaccharides primarily composed of glucose, arabinose, rhamnose, xylose, and galactose are pharmacologically active ingredients in Lilium. The pharmacological activities shown by polysaccharides from Lilium include antioxidant, anti-tumor, immunomodulatory, hypoglycemic, bacteriostatic, and radiation protection effects. This review provides a comprehensive summary of the distribution of Lilium medicinal resources in China, current extraction and purification methods of Lilium polysaccharide (LP), the strategies used for analyzing the polysaccharide structure and monosaccharide composition in LP, and the pharmacological activities and structural modification of LP. This review provides a basis for the development and clinical application of LP along with the conservation and utilization of Lilium resources.

Fermented lily bulbs by "Jiangshui" probiotics improves lung health in mice.

Limited application in protecting lung health is attributed to the low levels of active compounds in lily plant bulbs. This study focused on enhancing the active compounds by fermenting Lilium davidii (Lanzhou Lily) bulbs with Limosilactobacillus fermentum GR-3, isolated from Jiangshui. Lily fermented bulbs with strain GR-3 (LFB+GR-3) increased the bioavailability of hexadecanoic acid methyl ester, 22-tetrahydroxy-5alpha-cholestan-6-one-3-O-beta-d-allopyranoside, 22-O-(6-deoxy-Alpha-l-mannopyranosyl)-3-O-beta-d-glucopyranosyl-pregn-5-en-20-one, 1-O-trans-feruloylglycerol, and 3,4 dihydroxybenzoic acid. LFB+GR-3 fraction was employed to treat the mice model exposed to the carbon black nanoparticles (CBNPs). Immunohistochemical analysis revealed that the deposition of CBNPs and damages in lung tissues were limited in the LFB+GR-3 treatment group, while TNF-α, IL-10, and IL-6 were elevated by 6.9, 4.3, and 7 folds in the CBNP exposure group. In addition, Lactobacillus, Escherichia, Lactococcus, and Muribacter were dominant in the lung microbiota of LFB+GR-3 than the CBNP group. The use of probiotic fermented lily bulbs might be helpful in lung infection treatment.

Chemical constituents from the bulbs of Lilium davidii var. unicolor and anti-insomnia effect.

In this work, twenty-five water-soluble constituents were isolated from the bulbs of Lilium davidii var. unicolor, including two new compounds termed liliumtides A and B (1-2), and seventeen known compounds (3-4, 6-13, 15, 17, 21-25) isolated from the genus of Lilium for the first time. Their structures were established using high-resolution electrospray ionization mass spectroscopy and 1D and 2D nuclear magnetic resonance data. To confirm furtherly the absolute configuration of liliumtide A, and to accumulate enough sample to study the anti-insomnia effect, a total synthesis for liliumtide A was achieved by four steps. The pentobarbital-induced sleeping time test showed that compared with the blank control group, the liliumtide A decreased sleep latency and significantly increased the sleep time. These results suggested that liliumtide A could be investigated as a natural anti-insomnia lead compound in the pharmaceutical and food industries.

Integrative analysis of metabolome and transcriptome provide new insights into the bitter components of Lilium lancifolium and Lilium brownii.

Lilium, a perennial crop with great ornamental, medicinal and edible value, has been frequently used as functional food and medicine. Lilium lancifolium Thunb. (L. lancifolium) and Lilium brownii F.E.Brown var.viridulum Baker (L. brownii) are the most used medicinal species in China. However, the flavor compounds of these two species have not yet been clear. Here, metabolomics and transcriptome analysis were used to reveal the difference of the bitter substances of L. lancifolium and L. brownii. Qualitative results indicated that nine compounds are commonly existed in L. lancifolium and L. brownii, while nine compounds are unique in L. lancifolium and eight compounds are unique in L. brownii. Furthermore, quantitative results revealed that the content of regaloside A in L. lancifolium was nearly 2-7 folds higher than that of L. brownii, and the content of regaloside B in L. lancifolium was about 4-16 folds higher than that of L. brownii. Regaloside C and E were not detected in L. brownii. Transcriptome analysis showed that there were 90 unique genes up-regulated in L. lancifolium samples in the pathway of phenylpropanoid biosynthesis and 75 unique genes up-regulated in L. brownii samples, which could be related to the different content and chemical structure specificity of phenylpropanoid glycerol glucosides in L. lancifolium and L. brownii. The results of our in-deep research provide new insights into the bitter substances of L. lancifolium and L. brownii, and a further consideration for the chemical consistency and quality evaluation for Lilii bulbus.

In-depth exploration and comparison of chemical constituents from two Lilium species through offline two-dimensional liquid chromatography combined with multimode acquisition of high-resolution mass spectrometry.

Lilium lancifolium and Lilium brownii viridulum were two common cultivars of Lilium in China, which have been used as a source of food in ancient China, and as a traditional herbal medicine in most northern hemispheres countries continues today. However, only a few secondary metabolites in Lilium closely related to human health have been reported. In this research, an offline two-dimensional (HILIC and RP C18) separation system combined with multimode high-resolution mass spectrometry data acquisition was established for in-depth exploration and comparison of the chemical components in Lilium. In total, 331 components were identified, among which phenylpropanoid derivatives and steroidal saponins were the most abundant components. Furthermore, sulfur derivatives and steroidal alkaloids were systematically characterized in Lilium for the first time. These results provided valuable information for in-depth differentiating types of components characterization, which may be applied to assess and improve the edible and medicinal values of Lilium.

An optimized method to obtain high-quality RNA from different tissues in Lilium davidii var. unicolor.

The high quality, yield and purity total RNA samples are essential for molecular experiments. However, harvesting high quality RNA in Lilium davidii var. unicolor is a great challenge due to its polysaccharides, polyphenols and other secondary metabolites. In this study, different RNA extraction methods, namely TRIzol method, the modified TRIzol method, Kit method and cetyltrimethylammonium bromide (CTAB) method were employed to obtain total RNA from different tissues in L. davidii var. unicolor. A Nano drop spectrophotometer and 1% agarose gel electrophoresis were used to detect the RNA quality and integrity. Compared with TRIzol, Kit and CTAB methods, the modified TRIzol method obtained higher RNA concentrations from different tissues and the A260/A280 ratios of RNA samples were ranged from 1.97 to 2.27. Thus, the modified TRIzol method was shown to be the most effective RNA extraction protocol in acquiring RNA with high concentrations. Furthermore, the RNA samples isolated by the modified TRIzol and Kit methods were intact, whereas different degrees of degradation happened within RNA samples isolated by the TRIzol and CTAB methods. In addition, the modified TRIzol method could also isolate high-quality RNA from other edible lily bulbs. Taken together, the modified TRIzol method is an efficient method for total RNA isolation from L. davidii var. unicolor.

A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats.

CONTEXT: The bulb of Lilium brownii F. E. Brown (Liliaceae) (LB) is a common Chinese medicine to relieve insomnia. OBJECTIVE: To investigate the molecular mechanism of LB relieving insomnia. MATERIALS AND METHODS: Insomnia model was induced by intraperitoneally injection p-chlorophenylalanine (PCPA) in Wistar rats. Rats were divided into three groups: Control, PCPA (400 mg/kg, i.p. 2 days), LB (598.64 mg/kg, oral 7 days). The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE), melatonin (MT), and the expression of GABAA, 5-HT1A and MT receptors, as well as pathological changes in hypothalamus, were evaluated. 16S rDNA sequencing and UPLC-MS/MS were used to reveal the change of the intestinal flora and metabolic profile. RESULTS: The adverse changes in the abundance and diversity of intestinal flora and faecal metabolic phenotype altered by PCPA in rats were reversed after LB treatment, accompanied by the up-regulated levels of 5-HT as 8.14 ng/mL, MT as 16.16 pg/mL, 5-HT1A R and GABAA R, down-regulated level of NE as 0.47 ng/mL, and the improvement of pathological phenomena of cells in the hypothalamus. And the arachidonic acid metabolism and tryptophan metabolism pathway most significantly altered by PCPA were markedly regulated by LB. Besides, it was also found that LB reduced the levels of kynurenic acid related to psychiatric disorders and trimethylamine-N-oxide associated with cardiovascular disease. CONCLUSION: The mechanism of LB relieving insomnia involves regulating flora and metabolites to resemble the control group. As a medicinal and edible herb, LB could be considered for development as a health-care food to relieve increasing insomniacs in the future.

Three Previously Undescribed Chlorophenyl Glycosides from the Bulbs of Lilium regale.

Three previously undescribed chlorophenyl glycosides, (2,4,6-trichloro-3-hydroxy-5-methoxyphenyl)methyl ß-D-glucopyranoside (1), (2,4-dichloro-3,5-dimethoxyphenyl)methyl 6-O-ß-D-glucopyranosyl-ß-D-glucopyranoside (2) and 4-chloro-3-methoxy-5-methylphenyl 6-O-(6-deoxy-ß-L-mannopyranosyl)-ß-D-glucopyranoside (3) were obtained from Lilium regale. The absolute configurations of these new finds were elucidated by comprehensive analyses of spectroscopic data combined with acid hydrolysis derivatization. (2,4-dichloro-3,5-dimethoxyphenyl)methyl 6-O-ß-D-glucopyranosyl-ß-D-glucopyranoside (2) can inhibit the proliferation of lung carcinoma A549 cells with an IC50 value of 29 µΜ.

Metabolome-Based Discrimination Analysis of Five Lilium Bulbs Associated with Differences in Secondary Metabolites.

The bulbs of several Lilium species are considered to be both functional foods and traditional medicine in northern and eastern Asia. Considering the limited information regarding the specific bioactive compounds contributing to the functional properties of these bulbs, we compared the secondary metabolites of ten Lilium bulb samples belonging to five different species, using an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based secondary metabolomics approach. In total, 245 secondary metabolites were detected; further, more metabolites were detected from purple Lilium bulbs (217 compounds) than from white bulbs (123-171 compounds). Similar metabolite profiles were detected in samples within the same species irrespective of where they were collected. By combining herbal analysis and screening differential metabolites, steroid saponins were considered the key bioactive compounds in medicinal lilies. Of the 14 saponins detected, none were accumulated in the bulbs of L. davidii var. willmottiae, also called sweet lily. The purple bulbs of L. regale accumulated more secondary metabolites, and, notably, more phenolic acid compounds and flavonoids. Overall, this study elucidates the differential metabolites in lily bulbs with varying functions and colors and provides a reference for further research on functional foods and the medicinal efficacy of Lilium species.

Lily bulbs' polyphenols extract ameliorates oxidative stress and lipid accumulation in vitro and in vivo.

BACKGROUND: Polyphenols have the potential to reduce the risk of many metabolic disorders. Lily bulbs are rich in polyphenols; however, their effects on lipid metabolism remain unclear. This study aimed to explore the effects of lily bulbs' polyphenols (LBPs) on oxidative stress and lipid metabolism. RESULTS: A total of 14 polyphenolic compounds in LBPs were identified by high-performance liquid chromatography equipped with diode-array detection mass spectrometry. Total phenolic compound in LBPs was 53.76 ± 1.12 g kg-1 dry weight. In cellular experiments, LBPs attenuated the disruption of mitochondrial membrane potential, impeded reactive oxygen species production, alleviated oxidative stress, and reduced lipid accumulation in oleic acid induced HepG2 cells. In in vivo studies, LBPs significantly inhibited body weight gain, reduced lipid levels in serum and liver, and improved oxidative damage in a dose-dependent manner in mice fed a high-fat diet. Moreover, LBPs ameliorated hepatic steatosis and suppressed the expression of hepatic-lipogenesis-related genes (SREBP-1c, FAS, ACC1, and SCD-1) and promoted lipolysis genes (SRB1 and HL) and lipid oxidation genes (PPARα and CPT-1) in mice fed a high-fat diet. CONCLUSION: It was concluded that LBPs are a potential complementary therapeutic alternative in the development of functional foods to curb obesity and obesity-related diseases, such as metabolic syndrome. © 2021 Society of Chemical Industry.

Glucose absorption regulation and mechanism of the compounds in Lilium lancifolium Thunb on Caco-2 cells.

In this paper, the Caco-2 cell was used to study the glucose absorption regulation and mechanism of kaempferol, caffeic acid and quercetin-3-O-ß-D-galactoside in Lilium lancifolium Thunb in vitro. Glucose oxidase-peroxidase (GOD-POD) method was used to measure glucose consumption in supernatant. The fluorescent D-glucose analog (2-NBDG) was used as a tracer probe to study the changes in the fluorescence intensity of 2-NBDG uptake by Caco-2 cells with an inverted fluorescence microscope. Western blotting and quantitative real-time PCR were used to detect the protein expression and mRNA transcription of SGLT1 and GLUT2. The results showed that caffeic acid and quercetin-3-O-ß-D-galactoside could significantly promote the absorption of glucose by normal Caco-2 cells compared with the control group (P < 0.001). Both caffeic acid and quercetin-3-O-ß-D-galactoside could significantly promote the uptake of glucose tracer 2-NBDG on Caco-2 cells. Caffeic acid and quercetin-3-O-ß-D-galactoside could significantly promote SGLT1 and GLUT2 protein expression levels and mRNA transcription (P < 0.001, P < 0.01, P < 0.05). The mechanism might be related to the promotion of SGLT1 and GLUT2 protein expression levels and mRNA transcription.

Genus Lilium: A review on traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Lilium (family Liliaceae) is native to China and is mainly distributed in the temperate regions of the Northern Hemisphere such as Eastern Asia, Europe, and North America. There are about 109 species of this genus and 55 species in China. In America, the bulbs were used as food. In Europe, the petals and bulbs of Lilium candidum uesd as pectoral poultices, wound-healing remedy and a treatment for mastitis and shingles, the bulbs of L. martagon were used to treat every liver disease. In India, the bulbs are used medicinally as galactagogue, expectorant, aphrodisiac, diuretic, antipyretic and revitalizing tonic. In Asia, bulbs of this genus are often used to treat coughs, lung diseases, burns and swellings. AIM OF THE STUDY: The aim of this work was to summarize traditional uses, phytochemistry, pharmacology and toxicity, which provided a theoretical basis for the further study of Lilium plants and their applications in medicine, food and other industries. MATERIALS AND METHODS: Online scientific databases including Science Direct, American chemical society (ACS), Wiley Online Library, the Web of Science, China national knowledge internet (CNKI) and others were searched to identify eligible studies. More data were obtained from other Chinese medicine books. RESULTS: The literature survey revealed diverse traditional uses of the genus Lilium, mainly for the treatment of lung deficiency, hemostasis, anxiety, palpitations, asthma and vomiting. Over 180 compounds have been isolated and identified from the genus Lilium, including steroidal saponins, polysaccharides, phenolic glycerides, flavonoids and alkaloids. Different extracts and monomer compounds were so far evaluated for number of pharmacological activities including anti-tumor, anti-inflammatory, antioxidant, antibacterial, immunomodulatory, antidepressant and hepatoprotective activities. CONCLUSIONS: Lilium spp. are of much significance as ornamental flowers, but also have potential to treat various diseases, especially anti-inflammatory and antioxidant. However, most of the studies on pharmacological effects are still in in vitro, and further studies on mechanism-based pharmacological activities in vivo and in vitro are needed in the future. At present, there are limited researches on its safety and toxicological effects, which should be further explored.

Effects of different drying methods on the chemical constituents of Lilium lancifolium Thunb. based on UHPLC-MS analysis and antidepressant activity of the main chemical component regaloside A.

The Lilium lancifolium Thunb. is a herb with multiple functions in both medicine and food in China, and its extracts have shown antidepressant effects. In this study, fresh bulbs of Lilium lancifolium Thunb. were processed to study the effects of different drying processes on changes in its main chemical components. We found that different drying methods can affect the chemical constituents of the herb. Among these components, Regaloside A has been found as the characteristic component. Here, Cell Counting Kit-8 assay, and Western blotting were used to evaluate the neuroprotective antidepressant effects of Regaloside A. The results showed the cell survival rate was improved, the phosphorylation levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphatidylinositol 3 kinase, protein kinase B, and mammalian target of rapamycin were increased after Regaloside A treatment. In general, different drying methods have a significant influence on the chemical composition of the herb, and Regaloside A may be the main chemical component of the herb. It can alleviate the damage of corticosterone in SH-SY5Y cells, and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling mediated by brain-derived neurotrophic factor/tyrosine kinase receptor B may play an important role in the neuroprotective antidepressant effects of Regaloside A.