Traditional Uses and Pharmacologically Active Constituents of Dendrobium Plants for Dermatological Disorders:A Review

than 80 Dendrobium species have been reported in China.However,there are only six Dendrobium species,namely,D.bigibbum var.superbum(syn.D.phalaenopsis),D.chrysanthum,D.fimbriatum,D.loddigesii,D.nobile,and D.officinale(syn.D.candidum),listed in the New Inventory of Existing Cosmetic Ingredients in China Launched.Artificial planting of Dendrobium species has been a great success in China.To better utilize Dendrobium resources for medicinal and cosmetic purposes,we summarize their traditional uses and pharmacologically active compounds for treating dermatological disorders in this review.“Orchidaceae”,“Dendrobium”,“traditional use”,“ethnobotany”,“dermatological disorder”,and“skin disease”were used as search terms to screen the literature.Cited references were collected between 1970 and 2020 from the Web of Science,China National Knowledge Internet(CNKI),SciFinder,Google Scholar,and Chinese books.From the search,it was found that there are 22 Dendrobium species with traditional uses in dermatological disorders,and 131 compounds from Dendrobium plants have been reported to possess anti-inflammatory,antimicrobial,antioxidant,antiaging,anti-psoriasis,and tyrosinase-inhibitory activities,implying that Dendrobium plants are important resources for the discovery of active compounds and the development of new drugs and cosmetics.D.crepidatum,D.denneanum,D.loddigesii,D.nobile,and D.officinale have been extensively studied.More research on other Dendrobium species is needed.The major active compounds found in Dendrobium species are phenanthrenes,alkaloids,flavonoids,phenylpropanoids,and lignans.Several compounds,such as loddigesiinol A,(S)-5-methoxy-2,4,7,9-tetrahydroxy-9,10-dihydrophenanthrene,(S)-4-methoxy-2,5,7,9-tetrahydroxy-9,10-dihydrophenanthrene,2,5-dihydroxy-4-methoxy-phenanthrene 2-O-β-d-glucopyranoside,(9R)-1,2,5,9-tetrahydroxy-9,10-dihydrophenanthrene 5-O-β-d-glucopyranoside,(+)-homocrepidine A,and vicenin 2,have significant anti-inflammatory activities and inhibit nitric oxide(NO)production with IC_(50) values less than 5μM,and these compounds are worthy of further study.

Saponins from Paris forrestii(Takht.) H. Li displays potent activity against acute myeloid leukemia by suppressing RNF6/AKT/mTOR signaling pathway

Acute myeloid leukemia(AML) is a heterogeneous disease characterized by the accu.mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi.esis and ultimately resulting in bone marrow failure.Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years(5.3%) and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML.Saponins are amphipathic glycosides found in traditional Chinese medicines.In the present study,we isolated a panel of saponins from Paris forrestii(Takht.) H.Li,a unique plant found in Tibet and Yunnan provinces,China.By examining their activities in suppressing acute myeloid leukemia cell proliferation,total saponins from Paris forrestii(TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines.TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg.ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa.tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con.firmed by the inactivation of 4 EBP-1 and p70 S6 K,two typical downstream signal molecules in the AKT/mTOR pathway.More specifically,TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6,a recently identified oncogene in AML.RNF6 activated AKT/mTOR,and consistently,knockdown of RNF6 led to inactivation of the AKT/mTOR pathway.Furthermore,TSPf suppressed the growth of AML xenografts in nude mice models.Oral administration of 100 mg · kg^(-1) body weight almost fully suppressed tumor growth within 14 d,without gross toxicity.This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway.Given its low toxicity,TSPf could be developed for the treatment of AML.

Neolignans from Selaginella moellendorffii

Two new neolignans selaginellol(1)and selaginellol 4'-O-β-D-glucopyranoside(2),together with seven known compounds(3–9),were isolated from the whole plant of Selaginella moellendorffii.The structures of the new isolates were determined through spectroscopic data analysis.Compounds 1–9,as well as compounds 10–18 previously isolated from the species,were measured for the activity against platelet aggregation induced by ADP or collagen.Three neoligans(8,11,and 12),one flavanone(14),and one alkaloid(16)showed inhibitory activity against ADP-or collagen-induced platelet aggregation as compared with tirofiban.The dihydrobenzofuran neolignans(8,11,and 12)are more potent than the benzofuran neolignan(13)and other types of neolignans(1–7).Glucosidation of the dihydrobenzofuran neolignans(11 and 12)is helpful for the activity.Graphical Abstract Two new neolignans selaginellol(1)and selaginellol 40-O-b-D-glucopyranoside(2)were isolated from the whole plant of Selaginella moellendorffii.Several compounds from this plant showed the activity against platelet aggregation induced by ADP or collagen.

New amide alkaloids from Piper longum fruits

Three new amide alkaloids piperlongumamides A-C(1-3),together with 12 known ones(4-15),were isolated from the fruits of Piper longum.The structures of the new isolates were determined using spectroscopic data analyses.Cytotoxic activity of these amides against HL-60(human leukemia),A-549(human lung cancer),MCF-7(human breast cancer),SMMC-7721(human liver cancer)and SW480(human rectal cancer)cell lines were evaluated.Piperchabamide B(11)exhibited weak inhibitory activity against HL-60(IC_(50)=21.32μM),A-549(IC_(50)=23.82μM)and MCF-7(IC_(50)=16.58μM)cell lines.

Amides,Isoquinoline Alkaloids and Dipeptides from the Aerial Parts of Piper mullesua

One undescribedamide,pipermullesine A,twoundescribed isoquinoline alkaloids,pipermullesinesBand C,and six undescribed dipeptides,pipermullamides A–F,along with 28 known compounds,were isolated from the aerial parts of Piper mullesua.The structures of the undescribed compounds were elucidated based on the analysis of 1D and 2D NMR and MS data.Furthermore,the structures of pipermullesines A–Cwere confirmed by single crystal X-ray diffraction analysis.All isolates were evaluated for inhibitory activity against platelet aggregation induced by thrombin(IIa)or platelet-activating factor(PAF).(-)-Mangochinine,pellitorine,and(2E,4E)-N-isobutyl-2,4-dodecadienamide showed weak inhibitory activity against rabbit platelet aggregation induced by PAF,with IC_(50)values of 470.3μg/mL,614.9μg/mL,and 579.7μg/mL,respectively.

Chemical Constituents from the Whole Plant of Cuscuta reflexa

Two new 2H-pyran-2-one glucosides,cuscutarosides A(1)and B(2),and one new steroidal glucoside,7β-methoxy-β-sitosterol 3-O-β-glucopyranoside(3),together with 12 known compounds(4-15)were isolated from the whole plant of Cuscuta reflexa(Convolvulaceae)collected from Myanmar.The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis.The antiobesity activity of these isolates was evaluated using porcine pancreatic lipase(PPL),and the antiplatelet aggregation activity was screened using rabbit platelets induced by thrombin,platelet-activating factor(PAF),arachidonate(AA),or collagen.7β-Methoxy-β-sitosterol 3-O-β-glucopyranoside(3)showed weak PPL inhibitory activity.Cuscutaroside A(1),its acetylated derivative(1a),and scrophenoside B(8)showed weak inhibitory activity against rabbit platelet aggregation induced by collagen.Compound 1a also showed inhibitory activity against rabbit platelet aggregation induced by AA.

New Amides and Phenylpropanoid Glucosides from the Fruits of Piper retrofractum

Two new amides(E)-N-cinnamoyl-2-methoxypiperidine(1)and(R)-1-(2-oxopyrrolidin-3-yl)-5,6-dihydropyridin-2(1H)-one(2),four new amide glucosides,retrofractosides A-D(3-6),and two new phenylpropanoid glucosides,retrofractosides E(7)and F(8),together with 24 known compounds(9-32)were isolated from the fruits of Piper retrofractum.The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis.All of these isolates(1-32)were evaluated for inhibitory activity against mouse platelet aggregation induced by the peptide AYPGKF-NH2.(E)-N-(Tetrahydro-2H-pyran-2-yl)cinnamamide(9)showed a weak inhibitory efect,with an inhibition ratio of 52.0%at a concentration of 150μM.

Chemical Constituents from Ethanoic Extracts of the Aerial Parts of Leea aequata L.,a Traditional Folk Medicine of Myanmar

We aimed at reporting the chemical constituents and antimicrobial activities of Leea aequata L.,a traditional folk medicine used in Myanmar for the treatment of wounds and skin diseases.A new neolignan,(7S,8R)-9′-O-acetylcedrusin(1),a new lactam,(3S,4S)-4-chloro-3-hydroxypiperidin-2-one(2),along with 21 known compounds,including fve lignans(3-7),four favonoid glycosides(8-11),and others(12-23),were isolated from the ethanoic extract of the aerial parts of L.aequata.The structures of the new compounds were determined by NMR,MS,and ECD spectra.For all the antimicrobial tests of the 23 compounds,only 3,4,5-trihydroxybenzoic acid ethyl ester(17)showed weak inhibitory activities against Escherichia coli and Salmonella enterica subsp.enterica.

Five new 2-(2-phenylethyl)chromone derivatives and three new sesquiterpenoids from the heartwood of Aquilaria sinensis, an aromatic medicine in China

Five new 2-(2-phenylethyl)chromone derivatives,(5S,6R,7R,8S,7ʹR)-7ʹ-hydroxyagarotetrol(1),(5S,6R,7R,8S,7ʹS)-7ʹ-hydroxyagarotetrol(2),(6S,7S,8R)-2-[2-(4-methoxyphenyl)ethyl]-6,7,8-trihydroxy-5,6,7,8-tetrahydrochromone(3),(6S,7S,8R)-2-(2-phenylethyl)-6,7,8-trihydroxy-5,6,7,8-tetrahydrochromone(4),(5S,6R,7S,8R)-2-(2-phenylethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydro-8-[2-(2-phenylethyl)-7-methoxychromonyl-6-oxy]chromone(5),three new sesquiterpenoids,(4S,5S,7S,8S,10S,13R)-7,8,13-trihydroxyrotunda-1,11-dien-3-one(6),(4S,5S,7S,8S,10S,13S)-7,8,13-trihydroxyrotunda-1,11-dien-3-one(7),and(4R,5S,7S,8S,10S,13S)-7,8,13-trihydroxyrotunda-1,11-dien-3-one(8),along with 14 known compounds were isolated from the resinous heartwood of Aquilaria sinensis(Thymelaeaceae).The chemical structures of these new compounds were elucidated by 1D and 2D NMR and MS data,single-crystal X-ray diffraction analysis,and electronic circular dichroism(ECD)calculations.The neuroprotective activities of these isolates were evaluated using an in vitro model of rat adrenal pheochromocytoma(PC12)cell injury induced by corticosterone.At concentrations from 5 to 40μM,compounds 4 and 6,agarotetrol(9),and 6-hydroxy-2-(2-phenylethyl)chromone(17)showed significant protective activities against corticosterone-induced PC12 cell injury(P<0.001).

Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis

Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis(Lour.)Spreng.(Thyme-laeaceae)led to the isolation of a new cucurbitane-type triterpenoid,aquilarolide A(1),along with five known compounds(2-6).The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance(NMR)experiments and mass spectrometry(MS)data and theoretical calculations of its electronic circular dichroism(ECD)spectra.Aquilarolide A,cucurbitacin E(3),cucurbitacin B(4),and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(6)showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1,human lung squamous cell carcinoma NCI-H520,human lung adenocarcinoma A549,and paclitaxel-resistant A549(A549/Taxol)cell lines.All four active compounds,with IC_(50) values ranging from 0.002 to 0.91μM,had better inhibitory activities against A549/Taxol cells than paclitaxel(IC_(50)=1.80μM).Among them,cucurbitacin E(IC_(50)=0.002μM)is the most active.Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms.

Chemical constituents from heartwoods of Caesalpinia sappan with antiplatelet aggregation activities

Objective:To clarify the active constituents of the heartwoods of Caesalpinia sappan,a traditional Chinese medicine with the functions of promoting blood circulation(Huoxue in Chinese)and removing blood stasis(Quyu in Chinese).Methods:The chemical constituents were isolated and purified by combination of silica gel and Sephadex LH-20 column chromatography,along with semipreparative HPLC.Their chemical structures were established by multiple spectroscopic methods and comparison with literature data.The in vitro antiplatelet aggregation activities were evaluated using mouse platelet induced by AYPGKF-NH2,a gold agonist of protease-activated receptor 4(PAR4).Results:Two new phenols,methyl 2-(4,4’,5’-trihydroxy-2’-(methoxymethyl)biphenyl-2-yloxy)acetate(1)and 1’-methylcaesalpin J(2),together with 24 known compounds(3-26),were isolated from the heartwoods of C.sappan.Among them,sappanchalcone(16)and brazilin(20)showed inhibitory activities against mouse platelet aggregation with IC50 values of 114.8μmol/L and 100.8μmol/L,respectively.Conclusion:Antiplatelet compounds from C.sappan targeting at PAR4 are reported for the first time.