In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease.

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.

Discovery of a Novel Glucagon-like Peptide-1 (GLP-1) Analogue from Bullfrog and Investigation of Its Potential for Designing GLP-1-Based Multiagonists.

In this study, we aimed to discover novel GLP-1 analogues from natural sources. We investigated GLP-1 analogues from fish and amphibians, and bullfrog GLP-1 (bGLP-1) showed the highest potency. Starting with bGLP-1, we explored the structure-activity relationship and performed optimization and long-acting modifications, resulting in a potent analogue called 2f. Notably, 2f exhibited superior effects on food intake, glycemic control, and body weight compared to semaglutide. Furthermore, we explored the usefulness of bGLP-1 in designing GLP-1-based multiagonists. Using the bGLP-1 sequence, we designed novel dual GLP-1/glucagon receptor agonists and triple GLP-1/GIP/glucagon receptor agonists. The selected dual GLP-1/glucagon receptor agonist 3o and triple GLP-1/GIP/glucagon receptor agonist 4b exhibited significant therapeutic effects on lipid regulation, glycemic control, and body weight. Overall, our study highlights the potential of discovering potent GLP-1 receptor agonists from natural sources. Additionally, utilizing natural GLP-1 analogues for designing multiagonists presents a practical approach for developing antiobesity and antidiabetic agents.

The cytotoxicity of γδT cells in non-small cell lung cancer mediated via coordination of the BCL-2 and AKT pathways.

The effectiveness and mechanisms of γδT-cell immunotherapy in lung cancer remain unclear. In this study, we assessed the effects of continuous, low-dose γδT-cell intervention on lung cancer cells. We cultured γδT cells with a lung cancer cell line (A549) and replaced the γδT-cell population every 48 hours. The killing effect of γδTcells on A549 cells and the Half-maximal inhibitory concentration (IC50) value were detected by the cholecystokinin octapeptide (CCK-8) method. The levels of perforin, granzyme B and the inflammatory factors interleukin-6 (IL-6), interferon (IFN)-γ, and tumor necrosis factor-alpha (TNF-a), in the supernatants of cocultured cells were measured by ELISA. The protein expression of Bcl-2, Bax, PI3K and Akt was detected by western blotting. Our results indicated that γδT-cell treatment decreased the protein expression of Bcl-2, PI3K, and AKT but upregulated that of Bax. Moreover, γδT-cell treatment increased perforin and granzyme B release related to the Bax/Bcl-2 signaling pathway. In addition, γδT-cell-mediated cytolysis for A549 cells involved the PI3K/AKT pathway. In vivo results were consistent with the in vitro results. γδT-cell immunotherapy integrated regulation of a signaling pathway network involving the mutual regulation of apoptosis and proliferation. γδT-cell immunotherapy could be used to enhance the cytotoxic killing of lung cancer cells.

Three New Xanthones from Hypericum scabrum and Their Quorum Sensing Inhibitory Activities against Chromobacterium violaceum.

Quorum sensing (QS) plays an important role in the production of virulence factors and pathogenicity in pathogenic bacteria and is, therefore, a hopeful target to fight against bacterial infections. During our search for natural QS inhibitors, two new xanthonolignoids (1 and 2), each existing as a racemic mixture, one new simple oxygenated xanthone (7), and eight known analogs (3-6, 8-11) were isolated from Hypericum scabrum Linn. Chiral separation of 1 yielded a pair of enantiomers 1a and 1b. The structures of these compounds were elucidated by spectroscopic analysis and ECD (electrostatic circular dichroism) calculations. All isolates were evaluated for their QS inhibitory activity against Chromobacterium violaceum. Both 9 and 10 exhibited the most potent QS inhibitory effects with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 31.25 and 62.5 µM, respectively. Crystal violet staining was used to further evaluate the biofilm inhibition potential of compounds 7, 9 and 10, and the formation of biofilms increased with decreasing drug concentration in a classic dose-dependent manner. The results of a cytotoxicity assay revealed that compounds 7, 9 and 10 exhibited no cytotoxic activity on PC-12 cells at the tested concentration.

Insights into in vitro digestion properties and peptide profiling of Chinese rubing PDO cheese prepared using different acidification technology.

Rubing cheese is a traditional Chinese Protected Designation of Origin (PDO) cheese consumed for more than six hundred years, but to date, the digestion properties and peptide profiling during simulated gastrointestinal digestion are still uncertain. This study aimed to investigate the effects of traditional direct acidification technology (TRB) and fermentation acidification technology on digestion properties and peptide profiling of rubing cheese (FRB) proteins after simulated gastrointestinal digestion by protein digestomics, coupled with bioinformatic in silico analyses to identify potential bioactive peptides. The results demonstrated that FRB could significantly improve the in vitro digestibility, protein degradation, and polypeptide content than TRB (P ＜ 0.05). Furthermore, a total of 369 and 332 peptides were identified in FRB- and TRB-pancreatic digests, respectively, using LC-MS/MS. FRB could release more low molecular weight peptides of 400-1200 Da from α-casein and ß-casein after digestion. These low peptides included 16 reported potential ACEIPs (angiotensin I-converting enzyme inhibitory peptides), 11 dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides, and 6 antioxidant peptides, while TRB contained more than the reported potential antimicrobial peptides (10). In vitro activity determination showed that FRB had significantly higher ACEI, α-glucosidase inhibitory, and antioxidant activities than TRB during the entire digestion time (P ＜ 0.05), which was correlated to the reported potential bioactive peptides released during the digestion of FRB. Our study is the most comprehensive protein digestomic analysis of Chinese rubing cheese to date and provides a new positive outlook on rubing cheese consumption.

Monoterpenoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat, remove toxins, and treat obesity and diabetes, in Southwest China. The phytochemical research on the leaves of L. robustum led to the isolation and identification of eight new monoterpenoid glycosides (1-8) and three known monoterpenoid glycosides (9-11). Compounds 1-11 were tested for the inhibitory activities on fatty acid synthase (FAS), α-glucosidase, α-amylase, and the antioxidant effects. Compound 2 showed stronger FAS inhibitory activity (IC50: 2.36 ± 0.10 µM) than the positive control orlistat (IC50: 4.46 ± 0.13 µM), while compounds 1, 2, 5 and 11 displayed more potent ABTS radical scavenging activity (IC50: 6.91 ± 0.10~9.41 ± 0.22 µM) than the positive control L-(+)-ascorbic acid (IC50: 10.06 ± 0.19 µM). This study provided a theoretical basis for the leaves of L. robustum as a functional tea to treat obesity.

Childhood Socioeconomic Status and Depressive Symptoms of Young Adults: Mediating Role of Childhood Trauma.

Background: Studies have shown that low childhood socioeconomic status (SES) is associated with a high prevalence of depressive symptoms. Childhood trauma, as a potential consequence of low SES, may play an important part, but the mediation effect of childhood trauma remains to be elucidated. Methods: A cross-sectional survey was conducted among 1,807 university students. The MacArthur Scale of Subjective Social Economic Status-Youth Version, Childhood Trauma Questionnaire, and Beck Depression Inventory were used to measure childhood SES, childhood trauma, and current depressive symptoms, respectively. A structural equation model (SEM) was employed to demonstrate the mediating role of childhood trauma on the association between childhood SES and depressive symptoms. Results: The SEM demonstrated that childhood SES had significant indirect effects upon depressive symptoms via childhood trauma. Childhood trauma accounted for 89.3% of the total effect, indicating a profound mediation effect. Conclusions: The effect of childhood SES on the depressive symptoms of young adults was mediated by childhood trauma, which emphasizes the importance of early prevention and intervention of child neglect/abuse.

Astragalin Exerted Antidepressant-like Action through SIRT1 Signaling Modulated NLRP3 Inflammasome Deactivation.

Inflammation plays a key role in the pathogenesis of depression and antidepressant therapies. Astragalin (AST) is a bioactive flavonoid that possesses an anti-inflammatory property. However, the antidepressant action of astragalin has not been addressed. In this study, we explored the antidepressant effects of astragalin and its underlying mechanism. Our results showed that AST significantly improved the behavioral defects in chronic unpredictable mild stress (CUMS) model, promoted SIRT1 expression, and decreased the protein levels of NF-κB p65, NLRP3, cleaved capase-1, cleaved IL-1ß and cleaved gasdermin D in the hippocampus. Immunohistochemistry revealed AST mitigated CUMS-induced microglia overactivation. In vitro, AST profoundly increased the cell viability in lipopolysaccharides (LPS) and adenosine triphosphate (ATP) treated BV2 cells, with upregulated SIRT1 expression and downregulated protein levels of nuclear NF-κB p65, NLRP3, cleaved capase-1, and cleaved gasdermin D. Declined cleavage of gasdermin D was observed after AST administration in immunocytochemistry. Nevertheless, the in vivo and in vitro effects of AST were compromised by SIRT1 inhibitor EX-527. These results indicated that AST possessed an antidepressant property, which was dependent on SIRT1 signaling modulated NLRP3 inflammasome deactivation.

Effectiveness of Zhong-Yong thinking based dialectical behavior therapy group skills training versus supportive group therapy for lowering suicidal risks in Chinese young adults: A randomized controlled trial with a 6-month follow-up.

BACKGROUND: Dialectical behavior therapy (DBT) is a first-line treatment for the prevention of suicide. Zhong-Yong thinking could be viewed as a Chinese way of dialectical thinking, has long been a culturally dictating thinking style in China. To enhance cultural adaptability, we integrated Zhong-Yong thinking into DBT group skills training and examined its efficacy in suicidal prevention compared with a supportive group therapy and a wait-list group in high-risk suicidal Chinese college students. METHODS: A total of 97 suicidal participants were randomized to either Zhong-Yong thinking based DBT group skills training (DBTZYT , n = 33), or supportive group therapy (SGT; n = 32), or wait-list group (WL; n = 32). DBTZYT was a 12-week program based on Zhong-Yong thinking instead of dialectical thinking, coaching participants mindfulness, emotion regulation, distress tolerance, and interpersonal effectiveness. Supportive group therapy was a 12-week program aiming at improving interpersonal effectiveness and emotion regulation skills. Outcome measures were assessed at pre- and post-treatment and 6-month follow-up. RESULTS: At post-treatment measures, the levels of suicidal ideation, hopelessness, psychache symptoms, and general psychopathology had significantly decreased in both intervention groups; at the 6-month follow-up measures, the intervention effects were better maintained in the DBTZYT group rather than in the SGT group. Specifically, DBTZYT was more effective in relieving participants' long-term obsessive-compulsive, anxiety, hostility, phobic, psychotic, and additional symptoms. CONCLUSIONS: Zhong-Yong thinking not only could integrate with DBT skills training in Chinese young adult population, but also has special strength in enhancing DBT's efficacy.

Vasodilatory Effects of Aloperine in Rat Aorta and Its Possible Mechanisms.

The aim of this study was to investigate the vasodilatory effects of aloperine, one of main alkaloid was extracted from Sophora alopecuroides, on rat isolated thoracic aortic rings and its possible mechanisms. The isolated aortic arteries from normotensive Sprague Dawley rats were precontracted with phenylephrine (1 × 10⁻6 M) or KCl (60 mM). Then, aloperine (3.44 × 10⁻³ ­ 17.21 × 10⁻³ M) was added cumulatively and the tension curves was observed and recorded. The changes in tension in both endothelium-intact and endothelium-denuded aortic rings were also recorded. Afterwards, the interaction between aloperine with NG-nitro-L-arginine methylester (0.1 mM), indomethacin (1 × 10⁻³ mM), tetraethylammonium (10 mM), 4-aminopyridine (5 mM), BaCl2 (1 mM) and glibenclamide (0.01 mM) was evaluated. In this study, aloperine caused concentration-dependent relaxations in aortic rings precontracted with phenylephrine, but this effect was not observed in KCl-pretreated rings. Removal of endothelium showed no influence on vasodilatory effects of aloperine. In addition, preincubation with NG-nitro-L-arginine methylester and indomethacin did not inhibit the vasodilatory effects of aloperine, suggesting that the vasodilative action is endothelium-independent. Relaxant responses to aloperine were inhibited by tetraethylammonium and 4-aminopyridine. However, the vasorelaxant effect of aloperine was also not influenced by the preincubation with BaCl2 and glibenclamide. These findings suggest that aloperine-induced vasorelaxation effects are mainly due to the operations of voltage-operated potassium channels and ATP-sensitive potassium channels.

Spectral data of nicotabaflavonoidglycoside.

The dataset addressed in this article relates to the research article entitled"Nicotabaflavonoidglycoside, the first example of cembranoid and flavonoid heterodimer from Nicotiana tabacum" (Yang et al., 2018) [1]. The dataset presents the MS4(879-571-421-335), MS n fragment pathways, (+) HR-ESI-MS, (-) HR-ESI-MS, UV, IR, 1H NMR, 13C NMR, HSQC, 1H-1H COSY, HMBC, ROESY, ORD and ECD data of Nicotabaflavonoidglycoside. The MS4(879-571-421-335), (+) HR-ESI-MS, (-) HR-ESI-MS, UV, IR, 1H NMR, 13C NMR, HSQC, 1H-1H COSY, HMBC, ROESY, ORD and ECD data were collected by experimental methods, and the MSn fragment pathways were acquired by analyses.

Nicotabaflavonoidglycoside, the first example of cembranoid and flavonoid heterodimer from Nicotiana tabacum.

Nicotabaflavonoidglycoside (1), a novel cembrane-type diterpenoid and flavonoid heterodimer had been isolated from the leaves of Nicotiana tabacum. Its structure was elucidated as (1″S, 6″S) or (1″R, 6″R)-8-[6″-((-)-(1″S, 2″E, 4″Z, 7″E, 11″E)-cembra-2″, 4″, 7″, 11″-tetraenyl)]-rutin by comprehensive analyses of the NMR and HRESIMS spectra. Its absolute configurations of C-1″ and C-6″ were assigned as (1″S, 6″S) by its biogenesis and electronic circular dichroism (ECD). A possible biogenesis involving eliminate reaction of (1S, 2E, 4S, 6R, 7E, 11E)-2, 7, 11-cembratriene-4, 6-diol or its 4R isomer, as well as electrophilic substitution reaction of rutin was postulated.

[Chemical structure and bioactivity of cis-5'-oxopropylnicotine].

In this paper, the chemical constituents and bioactivities of leaves of Nicotiana tabacum were investigated. Six compounds were isolated by means of various chromatographic techniques (silica gel, Sephadex LH-20, MCI GEL CHP-20P and HPLC), and their structures were elucidated as cis-5'-(2-oxopropyl)-nicotine (1), 3-O-(9, 12, 15-octadecatrienoyl)-glyceryl-ß-D-galactppyranoside (2), (l'R, 2R, 5S, 10R)-2-(1', 2'-dihydroxy-l'-methylethyl)-6, 10-dimethylspiro [4, 5] dec-6-en-8-one (3), (l'S, 2R, 5S, l0R)-2-(1', 2'-dihydroxy-l'-methylethyl)-6, 10-dimethylspiro [4, 5] dec-6-en-8-one (4),2, 3-dihydroxypropyl-ß-D-galactoside (5) and phenylethyl ß-D-glucopyranoside (6) by extensive spectroscopic analyses (UV, IR, MS, 1D- and 2D-NMR). Among them, compound 1 is a new alkaloid, and compounds 2-6 are isolated for the first time from N. tabacum. Compounds 1 and 2 were assayed for agitating activities on transient receptor potential vanilloid 1 (TRPV1), melatonin receptor 1 and 2 (MT1 and MT2), 1 showed agitating rate of 55.41% (1.53mmol•L⁻¹) on MT2 and 2 possessed agitating rate of 128.11% (0.59 mmol•L⁻¹) and 52.00% (0.73mmol•L⁻¹) on TRPV1 and MT1, respectively.

Bioactivity-guided isolation of anti-hepatitis B virus active sesquiterpenoids from the traditional Chinese medicine: Rhizomes of Cyperus rotundus.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Cyperus rotundus (C. rotundus) is a well-known traditional Chinese medicine to cure hepatitis in many formulae, but the active components responsible for hepatitis have not been elucidated. According to our bioassay on HepG2.2.15 cell line in vitro, the ethanol extract of C. rotundus demonstrated potent anti-HBV activity. This current study was designed to isolate and identify the anti-HBV active constituents from the rhizomes of C. rotundus. MATERIAL AND METHODS: Bioactivity and LC-MS guided fractionation on the extract of C. rotundus using various chromatographic techniques including open-column, Sephadex LH-20 and semi-preparative high performance liquid chromatography led to the isolation and identification of thirty-seven sesquiterpenoids. Structural elucidation of the isolates was carried out by extensive spectroscopic analyses (UV, IR, HRMS, 1D- and 2D -NMR). The anti-HBV activity and cytotoxicity were evaluated on the HBV-transfected HepG2.2.15 cell line in vitro. The cytotoxicity effects of the isolates were assessed by a MTT assay. The secretions of HBsAg and HBeAg in the culture medium were detected by ELISA method, and the load of HBV DNA was quantified by real-time fluorescent PCR technique. RESULTS: Five new patchoulane-type sesquiterpenoids, namely cyperene-3, 8-dione (1), 14-hydroxy cyperotundone (2), 14-acetoxy cyperotundone (3), 3ß-hydroxycyperenoic acid (4) and sugetriol-3, 9-diacetate (5), along with 32 known sesquiterpenoids were isolated from the active fractions of C. rotundus. Compounds 2 and 3 were the first cyperotundone-type sesquiterpenoids with a hydroxyl group at C-14 position. Nine eudesmane-type sesquiterpenoids (15-21 and 23-24) significantly inhibited the HBV DNA replication with IC50 values of 42.7±5.9, 22.5±1.9, 13.2±1.2, 10.1±0.7, 14.1±1.1, 15.3±2.7, 13.8±0.9, 19.7±2.1 and 11.9±0.6 µM, respectively, of which, compounds 17, 21, 23 and 24 possessed high SI values of 250.4, 125.5,>259.6 and 127.5, respectively. Two patchoulane-type sesquiterpenoids (4 and 7) effectively suppressed the secretion of HBsAg in a dose-dependent manner with IC50 values of 46.6±14.3 (SI=31.0) and 77.2±13.0 (SI=1.7) µM, respectively. Compounds 2, 8, 12, 15, 17 and 25 possessed moderate activities against HBeAg secretion with IC50 values of 162.5±18.9 (SI=13.3), 399.2±90.0 (SI=10.6), 274.7±70.8 (SI=5.2), 313.9±87.5 (SI=7.2), 334.0±70.4 (SI=9.9) and 285.3±20.9 (SI=15.5) µM, respectively. CONCLUSIONS: This is the first study to reveal the anti-HBV constituents of C. rotundus, demonstrating that the eudesmane-type sesquiterpenoids might contribute to the anti-HBV activity of the rhizomes of C. rotundus.

Lignans from the Fruits of Melia toosendan and Their Agonistic Activities on Melatonin Receptor MT1.

Investigation on the fruits of Melia toosendan afforded seven new lignans (1-7), along with seventeen known compounds (8-24). The structures of the new compounds, involving four neo-lignans (1-4), two sesquilignans (5-6), and a nor-lignan (7), were elucidated based on extensive spectroscopic analyses (high-resolution electrospray ionization mass spectra, ultraviolet, infrared, one-dimensional and two-dimensional nuclear magnetic resonance). Compound 24 exhibited activity on melatonin receptor type 1 with an agonistic rate of 57.77% at 1.02 mM according to the assay on HEK293 cell lines in vitro.

[Chemical constituents of Lepidium meyenii].

To study the chemical constituents of Lepidium meyenii, the air-dried rhizome of L. meyenii was extracted with 70% EtOH. The extract was condensed to a small amount of volume and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isolated and purified by column chromatography, and identified based on spectral analyses (1H-NMR, 13C-NMR, HRESIMS). Eighteen compounds were isolated from L. meyenii, including 7 alkaloids and 4 fatty acids and 7 other compounds. They were characterized as (3-hydroxybenzyl) carbamic acid(1), phenylmethanamine(2), N-benzylformamide (3), N-benzylacetamide (4), pyridin-4-ylmethanamine(5), n-(4-methoxybenzyl) aniline(6), uracil(7), succininc acid(8), decanedioic acid(9), n-hexa- decanoic acid methyl ester(10), heptanoic acid(11), solerole(12), pyromucic acid methyl ester(13), 5-hydroxymethyl-2-furancar- boxadehyde(14), 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde(15), 1,7-dihydroxy-2,3, 4-trimethoxyxanthone (16), 1,7-di- hydroxy-3,4- dimethoxy-xanthone(17), (+)-pinoresinol(18). Meanwhile, compounds 1-18 were obtained from L. neyenii for the first time.

Two new sesquiterpenoid glycosides from Nicotiana tabacum.

Two new sesquiterpenoid glycosides, nicotabalactonecoside (1) and nicotabadiolcoside (2), along with four known terpenoids (3-6) were isolated from the leaves of Nicotiana tabacum. The structures of compounds 1 and 2 were determined as dihydrodeacetylphytuberin-2-one 11-O-ß-D-glucopyranoside and 1,2-dehydro-4-epieremophil-9-ene-11,12-diol 12-O-ß-D-glucopyranoside by extensive spectroscopic analyses (HR-ESI-MS, UV, IR, 1D, and 2D NMR) and chemical method. Compound 1 is an unusual phytuberin-type sesquiterpenoid with a 6/5/5 tricyclic system.

Noreudesmane sesquiterpenoids from the leaves of Nicotiana tabacum.

Six new 14-noreudesmane sesquiterpenoids, nicotabacosides A-F (1-6), along with five known sesquiterpenoids (7-11), were isolated from the leaves of Nicotiana tabacum. The structures of compounds 1-6 were elucidated as isorishitin 3-O-ß-D-glucopyranoside (1), rishitin 3-O-ß-D-glucopyranoside (2), rishitin 2-O-ß-D-glucopyranoside (3), 1, 6-dehydro-rishitin 3-O-ß-D-glucopyranoside (4), 2-hydroxyl-ligudentatol 3-O-ß-D-glucopyranoside (5) and oxyglutinosone 3-O-ß-D-glucopyranoside (6) based on extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). Their absolute configurations were determined by X-ray single-crystal diffraction and comparison of their electronic circular dichroism (ECD) spectra.

(±)-Paeoveitol, a pair of new norditerpene enantiomers from Paeonia veitchii.

(+)-Paeoveitol and (-)-paeoveitol, a pair of new norditerpene enantiomers, were isolated from the root of Paeonia veitchii. Their structures and absolute configurations were determined on the basis of extensive analysis of 1D and 2D NMR spectra, crystal X-ray diffraction, and electronic circular dichroism (ECD). A possible biogenesis involving two molecules of paeoniflorin was postulated.