Valeriana jatamansi: Bioactive Compounds and their Medicinal Uses.

Valeriana jatamansi is a reputed perennial medicinal herb distributed throughout the world, where it is used in cytotoxicity, neuronal problems, insomnia, leishmania and acetylcholinesterase inhibitor, antioxidant, antiviral and α-glucosidase inhibition activities. This review describes the current state of chemical characterization of isolated metabolites, which are well accepted for the treatment of various ailments in the indigenous system of medicine. This comprehensive review covers previously published research articles and reviews up to 2023 with an emphasis on the structural characterization of isolated bioactive compounds using different analytical techniques. Furthermore, the present review also focuses on the detailed medicinal and pharmacological properties of isolated compounds from this threatened herb.

Chemodiversity and α-Glucosidase Activity of Eucalyptus Species from Northwestern Himalaya, India.

The aim of current work was to determine essential oils (EOs) composition from three Eucalyptus species, including E. citriodora, E. camaldulensis and E. globulus and assess their α-glucosidase inhibitory activity. The EOs were collected using the hydrodistillation technique and characterized by GC/MS, GC-FID and NMR. The isolated EOs from leaves parts of Eucalyptus species varied from 0.56 to 1.0 % on fresh weight basis. The content of the EOs was distinct according to the species. The most abundant metabolites were identified as citronellal (0-83.0 %), 1,8-cineole (0.2-44.8 %), spathulenol (0.4-16.1 %) α-pinene (0.4-15.9 %), p-cymene (3.7-11.9 %), citronellol (0-8.6 %), ß-eudesmol (5.3-8.6 %) and ß-pinene (0-7.1 %). The EOs obtained from targeted samples exhibited strong α-glucosidase inhibitory activity. These results are encouraging and underline that the EOs of Eucalyptus species may be a promising alternative source of natural antidiabetic.

A new iridoid from the roots of Valeriana jatamansi Jones with α-glucosidase activity.

One new iridoid namely rupesin F (1) together with four known ones (2-5) were isolated from the roots of Valeriana jatamansi Jones. The structures were established using spectroscopic methods (1D and 2D NMR including HSQC, HMBC, COSY and NOESY) and by comparison with previously published literature data. The isolated compounds 1 and 3 exhibited strong α-glucosidase inhibition activity with IC50 values of 10.13 ± 0.11 and 9.13 ± 0.03 µg/mL, respectively. This study enriched the chemical diversity of metabolites and provides a direction for the development of antidiabetic agents.

Chemical profiling and α-glucosidase inhibitory activity of essential oils extracted with two methods from some North Western Himalayan aromatic crops.

Solvent-free hydrodistillation adsorption apparatus (HDA) and normal clevenger hydrodistillation (NC) were applied to obtain Juniperus communis, Valeriana jatamansi and Hedychium spicatum essential oils (EOs). The yields, chemical compositions and α-glucosidase inhibitory activity of the EOs were investigated. Obtained EOs were analyzed using gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) instruments. Recovery improvement was observed in HDA method (30.4%, 27.3% and 29.0% more recovery of EOs than NC method for V. jatamansi, H. spicatum and J. communis, respectively). Present results demonstrated NCV (V. jatamansi EO (essential oil) by NC method) had highest α-glucosidase inhibitory activity with half-maximal inhibitory concentration (IC50) values of 8.20 µg/mL. As a result, HDA method is considered to be the promising theme for producing EOs with high production recovery. Furthermore, current findings demonstrated that the selected EOs may be a good natural antidiabetic.

In vitro antidiabetic and antimicrobial activity of Dracocephalum heterophyllum Benth. essential oil from different sites of North-western Himalayas India.

Dracocephalum heterophyllum Benth (Lamiaceae) is a wild herb that possesses a number of biologically active phytomolecules. The aim of this study was to investigate comparative essential oils (EOs) composition and biological (antimicrobial and anti-diabetic) activities of D. heterophyllum from higher altitudes. Gas chromatography-mass spectrometry (GC/MS) and gas chromatography-flame ionisation detector (GC-FID) were carried out for the identification and quantification of EOs components. The hydrodistillation of fresh aerial part of D. heterophyllum gave (0.1-0.8) % w/v EOs yield. Altogether, twenty-seven constituents were identified in the among samples representing (91.0-98.2) % of the EOs composition. The ß-citronellol (31.5-83.7) % contributes major constituent in all samples. The in vitro antimicrobial potential of EOs was examined against six human pathogenic bacterial and two phytopathogens fungal strains. Anti-diabetic activity exhibits excellent α-amylase and better α-glucosidase enzymes inhibitor properties.

Chemical Diversity and α-Glucosidase Inhibitory Activity in Needles Essential Oils of Four Pinus Species from Northwestern Himalaya, India.

This work describes the study of the chemical profiling and α-glucosidase inhibitory activity of essential oils (EOs) from four Pinus species (P. wallichiana, P. patula, P. roxburghii and P. gerardiana). The identification and quantification of EOs metabolites were performed by GC/MS, GC-FID and 13 C-NMR. The needles of P. wallichiana and P. gerardiana presented the highest oil yields (0.35 % and 0.36 %, respectively). Twenty-four constituents were characterized in among samples exhibiting 93.8-97.7 % of the total EOs. The components and yields of the targeted samples were varied according to the species. Major components of the oils were α-pinene (20.5-34.1 %), ß-pinene (1.4-53.0 %), δ-3-carene (0.2-47.0 %), limonene (1.7-13.4 %), ß-phellandrene (0.2-23.4 %), ß-myrcene (1.8-7.2 %) and α-terpinolene (0.6-7.9 %). The extracted EOs showed strong α-glucosidase inhibitory activity, which was close to the positive control, acarbose. This study showed that the EOs of Pinus species may be used as natural antidiabetic.

Isocratic elution based analytical method for quantification of phytoconstituents in Hedychium spicatum and evaluation of their α-glucosidase inhibitory activity.

An efficient, fast, selective and simple isocratic elution method has been established using ultra performance liquid chromatography coupled to photodiode array detection and electrospray ionisation mass spectrometry (UPLC-PDA-ESI-MS) techniques for the quantification of isolated molecules from Hedychium spicatum rhizomes and assess their α-glucosidase inhibitory activity. Developed analytical method was validated as per the regulatory guidelines such as linearity, selectivity, the limits of detection (LOD) and quantification (LOQ), repeatability and accuracy. Highest concentration of 7-hydroxy hedychenone (4) (76.7 mg/g of dried plant material) was detected in rhizomes. Present results demonstrated parent extract (ethanolic) had the greatest inhibitory effect on α-glucosidase with IC50 values of 4.0 µg/mL. Developed method can be used as a new analytical approach for quality assessment of H. spicatum based herbal formulations and other products. Furthermore, current findings showed that the extract, fraction and isolated metabolites may be a good natural antidiabetic.

NMR based profiling of sesquiterpene lactones in Saussurea lappa roots collected from different location of Western Himalaya.

Saussurea lappa (Decne.) Sch.Bip is a well known herbal medicine has been extensively used for many therapeutic purposes. In this article, we have accomplished targeted profiling of S. lappa roots samples collected from different locations (Pangi, Lahaul, Barot and Kullu) of the western Himalayan region using NMR. This study allowed us to assigned four major sesquiterpenes of this plant, including costunolide (CL), dehydrocostus lactone (DCL), alantolactone (AL), isoalantolactone (IAL). Quantification of sesquiterpene lactones have also been accomplished using 1HNMR, and a wide diversity in the concentration of these active metabolites was observed. It has been observed that AL and IAL were major in the samples collected from Lahaul and Barot regions, and CL and DCL were major in the samples collected from Kullu and Pangi regions. This study concludes that S. lappa roots possess wide chemical diversity, which may be due to various biotic and abiotic environmental related factors.

New iridoids from the roots of Valeriana jatamansi Jones.

Two new iridoids namely valerialloside A and valerianoside A (1 and 2) along with five known compounds (3-7) were isolated from the roots of Valeriana jatamansi Jones. The structure of new compounds were determined using 1D and 2D NMR including 1H-1H COSY, HSQC, HMBC and NOESY spectroscopic techniques.

Phytochemical studies of Jurinea macrocephala roots from Western Himalaya.

Phytochemical investigation of the Jurinea macrocephala roots afforded six compounds namely ß-sitosterol (1), lupenone (2), physcion (3), ptiloepoxide (4), 20, 21α-epoxytaraxastan-3ß-ol (5) and chlorogenic acid (6). All the compounds were isolated for the first time in roots. The structures of the compounds were established by analysis of their spectroscopic (1H and 13C NMR) and spectrometric (MS) data, as well as by comparison of these with those reported in the literature. Metabolic profiling of chloroform and ethyl acetate fractions were also accomplished using NMR. In NMR analysis, ERETIC (electronic reference to access in-vivo concentration) 2 method was used for the quantification of identified metabolites. High quantity of chlorogenic acid (6, 130 mg/g) lupenone (2, 33.4 mg/g) and amyrins (α, ß) (170.6 mg/g) were detected in ethyl acetate and chloroform fractions. Further studies on the biological evaluation of phenolic-rich and chloroform fractions could be beneficial to explore its pharmaceutical potential.

An unprecedented N- to C-sulfonyl migration in the reaction of azomethine amine and allenoates: access to arylsulfonylmethyl substituted pyrazolo[1,5-c]quinazoline and mechanistic studies.

A serendipitous discovery of [1,3]-sulfonyl migration has been made in the two-component reaction of azomethine imine and allenoates. Current methodology involving N-S bond cleavage and C-S bond formation provided easy access to biologically important arylsulfonylmethyl substituted pyrazolo[1,5-c]quinazolines. Subsequently, a one-pot sequential protocol has been developed from the easily available starting material. The mechanistic investigation using quantum chemical methods revealed that the sulfonyl migration step is a concerted [1,3]-sigmatropic shift.

Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors.

A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 < 2.5 µM) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase.

Pd-Catalyzed Four-Component Sequential Reaction Delivers a Modular Fluorophore Platform for Cell Imaging.

A Pd-catalyzed cascade reaction of four versatile privileged synthons is described. The sequential reaction involves the formation of five new chemical bonds by concatenating three distinct chemical steps. One of the derivatives exhibited absorption in the visible region, fluorescence with a high quantum yield, and excellent photostability. Its application is explored in live cell imaging, which exhibited cytoplasmic and mitochondrial specific staining with no toxicity.

Synthesis of quinazoline-3-oxides via a Pd(ii) catalyzed azide-isocyanide coupling/cyclocondensation reaction.

A novel and efficient protocol concerning palladium catalyzing the three-component reaction of 2-azidobenzaldehyde, isocyanide, and hydroxylamine hydrochloride is developed. This method allows the rapid elaboration of quinazoline 3-oxides in a one-pot fashion. The 3-CR mainly involves concatenation of azide-isocyanide denitrogenative coupling, condensation with hydroxylamine and 6-exo-dig cyclization. The salient features of the methodology are operational simplicity, use of milder reaction conditions, being devoid of any additives such as oxidants (redox neutral) or base, and releasing N2 and H2O as the byproducts.

Iodine-catalyzed cross-coupling of isocyanides and thiols for the synthesis of S-thiocarbamates.

A novel and efficient metal free, redox-neutral method for the synthesis of secondary thiocarbamates by cross-coupling of readily available thiophenol and isocyanides has been developed. The present methodology exhibits a broad substrate scope with good to excellent yields without an additive/extra oxidant under mild reaction conditions catalyzed by inexpensive iodine as the catalyst.

UPLC-DAD quantification of chemical constituents of Potentilla atrosanguinea roots and their antioxidant activity.

Potentilla atrosanguinea, native to Himalayan region, is well known for its curative effects in traditional medicinal system. An ultra performance liquid chromatography-diode array detection method for the quantification of constituents of root part of P. atrosanguinea has been developed along with antioxidant activity evaluation. A simple and sensitive quantification method developed for seven compounds however only four compounds; p-coumaric acid (4), rutin (7), tiliroside (14) and kaempferol (16) were quantified as others were in lesser amount. Syringic acid and quercetin were found in trace amount whereas chlorogenic acid was absent in the ethanol extract of roots of P. atrosanguinea. Total polyphenolic and flavonoid contents were determined to be 21.75 mg of gallic acid equivalent and 8.57 mg of quercetin equivalent per gram of dry plant material, respectively. Antioxidant activity of extract was assessed using three assays; 2,2'-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing antioxidant power (FRAP). The IC50 values; 35.75 µg/ml and 30.35 µg/ml by DPPH and ABTS assays for ethanolic extract showed excellent free radical scavenging potential of its root part. The ferric reducing ability (FRAP) value, 26.67 mg of ascorbic acid per gram also indicated its higher antioxidant potential.

Relay tricyclic Pd(ii)/Ag(i) catalysis: design of a four-component reaction driven by nitrene-transfer on isocyanide yields inhibitors of EGFR.

Synthesis of pyrazolo[1,5-c]quinazolines from four easily available precursors is presented through a one-pot tricyclic Pd(ii)/Ag(i) relay catalysis. The bimetallic relay cascade forges five new chemical bonds by concatenating six discrete chemical steps. The relay catalysis enables four-component assembly of pyrazolo[1,5-c]quinazolines that selectively inhibit EGFR, exhibit apoptosis through the ROS-induced mitochondrial-mediated pathway, and arrest the cell cycle at the G1 phase.

Sequential Pd(0)/Fe(III) Catalyzed Azide-Isocyanide Coupling/Cyclization Reaction: One-Pot Synthesis of Aminotetrazoles.

A rapid and efficient synthesis of aminotetrazole from aryl azides, isocyanides, and TMSN3 is developed. The reaction is promoted by sequential Pd(0)/Fe(III) catalysis. The reaction sequence utilizes the Pd-catalyzed azide-isocyanide denitrogenative coupling reaction to generate unsymmetric carbodiimide in situ, which reacts with TMSN3 in the presence of FeCl3 in a single pot. The methodology has distinct advantages over traditional synthetic approaches where toxic Hg and Pb salts are employed at stoichiometric scale.

Chemical Composition, Cytotoxic and Antibacterial Activities of Essential Oils of Cultivated Clones of Juniperus communis and Wild Juniperus Species.

Needles of seven cultivated clones (C1 - C7) of Juniperus communis at lower altitude and three wild Juniperus species (J. communis, J. recurva and J. indica) at higher altitudes were investigated comparatively for their essential oils (EOs) yields, chemical composition, cytotoxic and antibacterial activities. The EOs yields varied from 0.26 to 0.56% (v/w) among samples. Sixty-one volatile components were identified by gas chromatography-mass spectrometry (GC/MS) and quantified using gas chromatography GC (FID) representing 82.5 - 95.7% of the total oil. Monoterpene hydrocarbons (49.1 - 82.8%) dominated in all samples (α-pinene, limonene and sabinene as major components). Principal component analysis (PCA) of GC data revealed that wild and cultivated Juniperus species are highly distinct due to variation in chemical composition. J. communis (wild species) displayed cytotoxicity against SiHa (human cervical cancer), A549 (human lung carcinoma) and A431 (human skin carcinoma) cells (66.4 ± 2.2%, 74.4 ± 1.4% and 57.4 ± 4.0%), respectively, at 200 µg/ml. EOs exhibited better antibacterial activity against Gram-positive bacteria than against Gram-negative bacteria with the highest zone of inhibition against Staphylococcus aureus MTCC 96 (19.2 ± 0.7) by clone-7. As per the conclusion of the findings, EOs of clone-2, clone-5 and clone-7 can be suggested to the growers of lower altitude, as there is more possibility of uses of these EOs in food and medicinal preparations.

A new oxo-sterol derivative from the rhizomes of Costus speciosus.

Chemical investigation of the rhizomes of Costus speciosus led to the isolation of a new compound, 22-ketocholesteryl palmitate (1) along with four known compounds, 24-methylenecycloartanol (2), cycloartanol (3), stigmasterol (4) and linoleic acid (5). The structure of new compound was characterised by extensive 1D-, 2D-NMR and mass spectrometry (GC-MS and HR-ESI-MS) techniques.