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Sandalwood essential oil is extracted from the heartwood part of mature sandalwood and is known for its pleasant fragrance and exceptional medicinal activities, including antimicrobial, antitumor, and anti-inflammatory properties. The (Z)-α-santalol and (Z)-β-santalol are the most vital ingredients contributing to sandalwood oil's bioactivities and unique woody odor characteristics. Metabolic engineering strategies have shown promise in transforming microorganisms such as yeast and bacteria into effective cell factories for enhancing the production of vital sesquiterpenes (santalene and santalol) found in sandalwood oil. This review aims to summarize sources of sandalwood oil, its components/ingredients, and its applications. It also highlights the biosynthesis of santalene and santalol and the various metabolic engineering strategies employed to reconstruct and enhance santalene and santalol biosynthesis pathways in heterologous hosts.

The biogenic approach for the synthesis of metal nanoparticles provides an efficient eco-friendly alternative to chemical synthesis. This study presents a novel route for the biosynthesis of silver nanoparticles using aqueous sandalwood (SW) leaf extract as a source of reducing and capping agents under mild, room temperature synthesis conditions. The bioreduction of Ag+ to Ago nanoparticles (SW-AgNPs) was accompanied by the appearance of brown color, with surface plasmon resonance peak at 340-360 nm. SEM, TEM and AFM imaging confirm SW-AgNP's spherical shape with size range of 10-32 nm. DLS indicates a hydrodynamic size of 49.53 nm with predominant negative Zeta potential, which can contribute to the stability of the nanoparticles. FTIR analysis indicates involvement of sandalwood leaf derived polyphenols, proteins and lipids in the reduction and capping of SW-AgNPs. XRD determines the face-centered-cubic crystalline structure of SW-AgNPs, which is a key factor affecting biological functions of nanoparticles. This study is novel in using cell culture methodologies to evaluate effects of SW-AgNPs on proliferating cells originating from plants and human cancer. Exposure of groundnut calli cells to SW-AgNPs, resulted in enhanced proliferation leading to over 70% higher calli biomass over control, enhanced defense enzyme activities, and secretion of metabolites implicated in biotic stress resistance (Crotonyl isothiocyanate, Butyrolactone, 2-Hydroxy-gamma-butyrolactone, Maltol) and plant cell proliferation (dl-Threitol). MTT and NRU were performed to determine the cytotoxicity of nanoparticles on human cervical cancer cells. SW-AgNPs specifically inhibited cervical cell lines SiHa (IC50-2.65 ppm) and CaSki (IC50-9.49 ppm), indicating potential use in cancer treatment. The opposing effect of SW-AgNPs on cell proliferation of plant calli (enhanced cell proliferation) and human cancer cell lines (inhibition) are both beneficial and point to potential safe application of SW-AgNPs in plant cell culture, agriculture and in cancer treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gowda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis , the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as "sandalwood oils". Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols ( Z )-α- and ( Z )-β-santalol were isolated from the S. album oil by column chromatography on AgNO 3 -coated silica. They were tested as isolated compounds against the fungus, and ( Z )-α-santalol was about two times more active than the β-isomer.

Santalum genus belongs to the family of Santalaceae, widespread in India, Australia, Hawaii, Sri Lanka, and Indonesia, and valued as traditional medicine, rituals and modern bioactivities. Sandalwood is reported to possess a plethora of bioactive compounds such as essential oil and its components (α-santalol and β-santalol), phenolic compounds and fatty acids. These bioactives play important role in contributing towards biological activities and health-promoting effects in humans. Pre-clinical and clinical studies have shown the role of sandalwood extract as antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, neuroleptic, antihyperglycemic, antihyperlipidemic, and anticancer activities. Safety studies on sandalwood essential oil (EO) and its extracts have proven them as a safe ingredient to be utilized in health promotion. Phytoconstituents, bioactivities and traditional uses established sandalwood as one of the innovative materials for application in the pharma, food, and biomedical industry., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Santalenes and santalols from Santalum album are the main components of the valuable spice sandalwood essential oil, which also has excellent pharmacological activities such as antibacterial, anti-inflammatory, and antitumor. Firstly, we constructed biosynthesis pathways of santalenes by synthetic biology strategy. The assembled biosynthetic cassettes were integrated into the multiple copy loci of δ gene in S. cerevisiae BY4742 with assistance of pDi-CRISPR, and 94.6 mg/L santalenes was obtained by shake flask fermentation of engineered yeast. Secondly, a selected optimized P450-CPR redox system was integrated into the chromosome of the santalenes-producing strain with a single copy, and 24.6 mg/L santalols were obtained. Finally, the yields of santalenes and santalols were increased to 164.7 and 68.8 mg/L, respectively, by downregulating ERG9 gene. This is the first report on the de novo synthesis of santalols by P450-CPR chimera in S. cerevisiae. Meanwhile, the optimized chimeric CYP736A167 opt -46tATR1 opt exhibits higher activity to oxidize santalenes into santalols. It would provide a feasible solution for the optimal biosynthesis of santalols. KEY POINTS: • First-time de novo synthesis of santalols by P450-CPR chimera in S. cerevisiae. • Truncated 46tATR1 has higher activity than that of CPR2. • Yields of santalenes and santalols were increased by downregulating ERG9 gene., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sandalwood oils are highly desired but expensive, and hence many counterfeit oils are sold in high street shops. The study aimed to determine the content of oils sold under the name sandalwood oil and then compare their chromatographic profile and α- and β santalol content with the requirements of ISO 3518:2002. Gas chromatography with mass spectrometry analysis found that none of the six tested "sandalwood" oils met the ISO standard, especially in terms of α-santalol content. Only one sample was found to contain both α- and β-santalol, characteristic of Santalum album . In three samples, valerianol, elemol, eudesmol isomers, and caryophyllene dominated, indicating the presence of Amyris balsamifera oil. Another two oil samples were found to be synthetic mixtures: benzyl benzoate predominating in one, and synthetic alcohols, such as javanol, polysantol and ebanol, in the other. The product label only gave correct information in three cases: one sample containing Santalum album oil and two samples containing Amyris balsamifera oil. The synthetic samples described as 100% natural essential oil from sandalwood are particularly dangerous and misleading to the consumer. Moreover, the toxicological properties of javanol, polysantol and ebanol, for example, are unknown.

Neuroinflammation is an inflammatory response in the nervous system that is associated with various neurological diseases including Alzheimer's diseases and others. Many studies evaluated the anti-inflammatory potential of Santalum album (S. album) extract, but none of them analyzed its effects against neuroinflammatory response in vitro. In addition, the precise mechanism underlying the anti-inflammatory effect of the extract has not yet been elucidated. Therefore, in this study, we investigated the effect of S. album extract on modulation of toll-like receptor 3 (TLR3) agonist polyinosnic-polycytidylic acid (PolyI:C)-induced neuroinflammatory response in human neuroblastoma cells. The TLR3-mediated immune response was differentially modulated by S. album extract in SH-SY5Y cells. In addition, treatment of cells with the conditioned medium (CM) of S. album extract significantly increased the mRNA levels of IFN-β, IFN-α, MxA and OAS-1 and decreased IL-6, CXCL8, CCL2 and IP-10. S. album extract has indirectly affected the expression of IFNs and inflammatory cytokines in SH-SY5Y cells. Furthermore, the extract was able to modulate PolyI:C-induced inflammatory response in Caco2 cells. Overall, S. album was capable to attenuate PolyI:C-induced neuroinflammatory effect through the induction of TLR2, TLR4 and the modulation of TLR negative regulators of the TRAF3, IRF3 and NF-κB pathways., (© 2020 John Wiley & Sons Ltd.)

Sandalwood (santalum spicatum) seed oil (SSO) is rich in ximenynic acid. The aim of the present study was to investigate the effect of SSO on high-fat/high-sucrose diet (HFHSD) induced insulin resistance (IR) in comparison with fish oil (FO), sunflower oil (SO) and linseed oil (LO). Fifty male Sprague-Dawley rats were randomly divided into five dietary groups: standard chow diet (controls), HFHSD plus 7% SSO, HFHSD plus 7% FO, HFHSD plus 7% SO and HFHSD plus 7% LO. After 12 weeks of feeding, the rats were sacrificed, and the serum parameters, hepatic lipids and underlying molecular mechanisms were studied. SSO, FO or LO significantly prevented glucose intolerance, hyperglycaemia, obesity, and hepatic lipid accumulation, and decreased the homeostasis model assessment of IR (HOMA-IR) and the serum levels of pro-inflammatory factors (IL-6, IL-1β and TNF-α) compared with SO. In addition, SSO activated the PI3K/AKT insulin signaling pathway and down-regulated the JNK/NF-κB inflammatory signaling pathway in the liver. In summary, our results proved that SSO exerted an ameliorative effect on IR by regulating the hepatic inflammation related blockage of the insulin signaling pathway in the rats.

Sandalwood is one of the most valuable woods in the world. However, today's counterfeits are widespread, it is difficult to distinguish authenticity. In this paper, similar genus (Dalbergia and Pterocarpus) and confused species (Gluta sp.) of sandalwood were quickly and efficiently identified. Rapid identification model based on 1 H NMR and decision tree (DT) algorithm was firstly developed for the identification of sandalwood, and the accuracy was improved by introducing the AdaBoost algorithm. The accuracy of the final model was above 95%. And the feature components between different species of sandalwood were further explored using UHPLC-QTOFMS and NMR spectrometry. The results showed that 183 compounds were identified, among which 99 were known components, 84 were unknown components. The 1 H NMR and 13 C NMR signals of 505 samples were assigned, among them, 14 compounds were attributed, characteristic chemical shift intervals with great differences in the model were analysed. Furthermore, the fragmentation pattern of different compounds from sandalwood, in both positive and negative ion ESI modes, was summarized. The results showed a potential and rapid tool based on DT, NMR spectroscopy and UHPLC-QTOFMS, which had performed great potential for rapid identification and feature analysis of sandalwood., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Upon screening compounds having Wnt signal inhibitory activity through evaluating TCF/β-catenin transcriptional (TOP) activity, eight cadinane sesquiterpenoids, including three new compounds (1-3), were isolated from wood extracts of Santalum album (Santalaceae). Structures of compounds 1-3 were elucidated by spectral data to have a cadinane skeleton with an aromatic ring. Of the eight compounds isolated, compound 4, identified as mansonone I, was found to be active against TOP, having an IC 50 of 1.2 μM.

Natural products from plants, such as chemopreventive agents, attract huge attention because of their low toxicity and high specificity. The rational drug design in combination with structure-based modeling and rapid screening methods offer significant potential for identifying and developing lead anticancer molecules. Thus, the molecular docking method plays an important role in screening a large set of molecules based on their free binding energies and proposes structural hypotheses of how the molecules can inhibit the target. Several peptide-based therapeutics have been developed to combat several health disorders, including cancers, metabolic disorders, heart-related diseases, and infectious diseases. Despite the discovery of hundreds of such therapeutic peptides however, only few peptide-based drugs have made it to the market. Moreover, the in silico activities of cyclic peptides towards molecular targets, such as protein kinases, proteases, and apoptosis related proteins have not been extensively investigated. In this study, we explored the in silico kinase and protease inhibitor potentials of cyclosaplin, and studied the interactions of cyclosaplin with other apoptosis-related proteins. Previously, the structure of cyclosaplin was elucidated by molecular modeling associated with dynamics that were used in the current study as well. Docking studies showed strong affinity of cyclosaplin towards cancer-related proteins. The binding affinity closer to 10 kcal/mol indicated efficient binding. Cyclosaplin showed strong binding affinities towards protein kinases such as EGFR, VEGFR2, PKB, and p38, indicating its potential role in protein kinase inhibition. Moreover, it displayed strong binding affinity to apoptosis-related proteins and revealed the possible role of cyclosaplin in apoptotic cell death. The protein-ligand interactions using LigPlot displayed some similar interactions between cyclosaplin and peptide-based ligands, especially in case of protein kinases and a few apoptosis related proteins. Thus, the in silico analyses gave the insights of cyclosaplin being a potential apoptosis inducer and protein kinase inhibitor., Competing Interests: The authors declare no conflict of interest.

Backgrounds: The chemical composition of many essential oils indicates that they have sedative and hypnotic effects, but there is still a lack of systematic studies on the sedative and hypnotic effects of essential oils. In addition, aromatherapy does not seem to have the side effects of many traditional psychotropic substances, which is clearly worthwhile for further clinical and scientific research. The clinical application of essential oils in aromatherapy has received increasing attention, and detailed studies on the pharmacological activities of inhaled essential oils are increasingly needed., Hypothesis/purpose: As insomniacs are usually accompanied by symptoms of depression and anxiety of varying degrees, based on the theory of aromatherapy of Traditional Chinese Medicine, this experiment is to study a Compound Anshen essential oil that is compatible with Lavender essential oil, Sweet Orange essential oil, Sandalwood essential oil and other aromatic medicine essential oils with sedative and hypnotic effects, anti-anxiety and anti-depression effects. To study the sedative and hypnotic effects of Compound Anshen essential oil inhaled and the main chemical components of Compound Anshen essential oil, and to compare and analyze the pharmacodynamics of diazepam, a commonly used drug for insomnia., Methods: The Open field test and Pentobarbital-induced sleep latency and sleep time experiments were used to analyze and compare the sedative and hypnotic effects of inhaling Compound Anshen essential oil and the administration of diazepam on mice. The changes of 5-HT and GABA in mouse brain were analyzed by Elisa. The main volatile constituents of Compound Anshen essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS)., Results: Inhalation of Compound Anshen essential oil can significantly reduce the spontaneous activity of mice, reduce latency of sleeping time and prolong duration of sleeping time. The results of enzyme-linked immunosorbent assay showed that Compound Anshen essential oil can increase the content of 5-HT and GABA in mouse brain. The main volatile chemical constituents of the Compound Anshen essential oil are D-limonene (24.07%), Linalool (21.98%), Linalyl acetate (15.37%), α-Pinene (5.39%), and α-Santalol (4.8%)., Conclusion: The study found that the inhalation of Compound Anshen essential oil has sedative and hypnotic effect. This study provides a theoretical basis for further research and development of the sedative and hypnotic effects of Compound Anshen essential oil based on the theory of aromatherapy.

This study aimed to determine the antimicrobial activity of 247 essential oil combinations against the reference strains of wound pathogens. Essential oil combinations were investigated for antimicrobial activity against five pathogens. The minimum inhibitory concentration (MIC) assay was used and the fractional inhibitory concentration index (ΣFIC) calculated to determine interactions between selected oils. Twenty-six combinations displayed broad-spectrum antimicrobial activity against all five reference strains and several displayed synergy against more than one pathogen. The combination of Santalum austrocaledonicum (sandalwood) with Commiphora myrrha (myrrh) displayed noteworthy antimicrobial activity against all five reference strains and synergy against four (MIC values 0.03-1.00 mg/ml and ΣFIC values 0.19-1.00 mg/ml) pathogens. No antagonism was observed. Santalum spp. and Vetiveria zizanioides essential oils contributed the most to antimicrobial activity in combination. Essential oil combinations are presented as a viable option in wound therapy., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

This paper presents a method for predicting the total nitrogen content in sandalwood using digital image processing. The goal of this study is to provide a real-time, efficient, and highly automated nutritional diagnosis system for producers by analyzing images obtained in forests. Using images acquired from field servers, which were installed in six forest farms of different cities located in northern Hainan Province, we propose a new segmentation algorithm and define a new indicator named "growth status" (GS), which includes two varieties: GSMER (the ratio of sandalwood pixels to the minimum enclosing rectangle pixels) and GSMCC (the ratio of sandalwood pixels to minimum circumscribed circle pixels). We used the error-in-variable model by considering the errors that exist in independent variables. After comparison and analysis, the obtained results show that (1) The b and L channels in the Lab color system have complementary advantages. By combining this system with the Otsu method, median filtering and a morphological operation, sandalwood can be separated from the background. (2) The fitting degree of the models improves after adding the GS indicator and shows that GSMCC performs better than GSMER. (3) After using the error-in-variable model to estimate the parameters, the accuracy and precision of the model improved compared to the results obtained using the least squares method. The optimal model for predicting the total nitrogen content is [Formula: see text]. This study demonstrates the use of Internet of Things technology in forestry and provides guidance for the nutritional diagnosis of the important sandalwood tree species., Competing Interests: The authors have declared that no competing interests exist.

Santalene and santalol are the main components of valuable perfume sandalwood essential oil, and have good antibacterial, anti-oxidation and anti-tumor activities. Commercial sandalwood essential oil is mainly extracted from sandalwood tree that grows slowly and is difficult to cultivate. In addition, the extraction recovery of sandalwood essential oil from sandalwood tree is too low to meet the market demand. These factors make sandalwood essential oil expensive. An option is to use genetic engineering and molecular biological methods to heterologously express related synthase of santalene and santalol in microbial host. In this paper, the biosynthesis progress of santalene and santalol synthase, as well as the optimization of mevalonate metabolic pathways in the hosts are summarized. Furthermore, the strategies of applying protein engineering technology to carry out orthomutation of santalene synthase were also discussed, to provide reference for the optimal biosynthesis of santalene and santalol.

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n -hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and β-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum . Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections., Competing Interests: The authors declare no conflict of interest.

West Australian sandalwood ( Santalum spicatum ) has long been exploited for its fragrant, sesquiterpene-rich heartwood; however sandalwood fragrance qualities vary substantially, which is of interest to the sandalwood industry. We investigated metabolite profiles of trees from the arid northern and southeastern and semi-arid southwestern regions of West Australia for patterns in composition and co-occurrence of sesquiterpenes. Total sesquiterpene content was similar across the entire sample collection; however sesquiterpene composition was highly variable. Northern populations contained the highest levels of desirable fragrance compounds, α- and β-santalol, as did individuals from the southwest. Southeastern populations were higher in E , E -farnesol, an undesired allergenic constituent, and low in santalols. These trees generally also contained higher levels of α-bisabolol. E , E -farnesol co-occurred with dendrolasin. Contrasting α-santalol and E , E- farnesol chemotypes revealed potential for future genetic tree improvement. Although chemical variation was evident both within and among regions, variation was generally lower within regions. Our results showed distinct patterns in chemical diversity of S. spicatum across its natural distribution, consistent with earlier investigations into sandalwood population genetics. These results are relevant for plantation tree improvement and conservation efforts.

In the fields of essential oils and fragrances, samples often consist of mixtures of compounds with similar structural and physical characteristics (e.g. mono- and sesquiterpenoids), whose correct identification closely depends on the synergic combination of chromatographic and mass spectral data. This sample complexity means that new GC stationary phases with different selectivities are continually being investigated. Ionic liquids (ILs) are of great interest as GC stationary phases in this field because of their selectivity (significantly different than that of currently phases) and their high temperature stability. A first generation of IL GC columns was found to be competitive when applied to these field, in terms of selectivity and efficiency, compared to conventional columns (polydimethylsiloxane, (e.g. OV-1), methyl-polysiloxane 5%-phenyl (e.g. SE-52), 7%-cyanopropyl, 7%-phenyl polysiloxane (e.g. OV-1701), and polyethylen glycol (e.g. PEG-20M). However, these columns showed significant activity towards polar or active analytes, which primarily affected their quantitative performance. A new generation of highly-inactive columns coated with three of the most widely-used ionic liquid GC stationary phases has recently been introduced; these phases are SLB-IL60i (1,12-di(tripropylphosphonium) dodecane bis(trifluoromethylsulfonyl) imide [NTf 2 ], SLB-IL76i (tri-(tripropylphosphonium-hexanamido)-triethylamine [NTf 2 ]), and SLB-IL111i (1,5-di (2,3-dimethyllimidazolium) pentane [NTf 2 ]). This study carefully tested the new inert IL columns, in view of their routine application in the fragrance and essential oil fields. They were found to have unusually high selectivity, comparable to that of first-generation IL columns, while their inertness and efficiency were competitive with those of currently-used conventional columns. The IL column performance of first and second generations was compared, through the quali-quantitative analysis of components in a group of different complexity samples; these included the Grob test, a standard mixture of "suspected" skin allergens, and the essential oils of chamomile and sandalwood., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: 'Ubtan' is a traditional herbal formulation in the Indian system of medicine being used in India and its subcontinent for a long time. Several commercial skin care formulations are marketed throughout this region as the name of Ubtan. Therefore, it is worthwhile to evaluate Ubtan in respect of its efficacy as skin care formulation., Aim of the Study: The present study was designed for the preparation of Ubtan and standardization through the chromatographic techniques by using suitable phyto-markers. Further, its antioxidant, sun protection factor (SPF) and anti-tyrosinase potential have been explored., Materials and Methods: Four in-house formulations (UF-1, UF-2, UF-3 and UF-4) were prepared by mixing a varied quantity of each powdered plants, i.e. turmeric (Curcuma longa L.), Chickpea (Cicer arietinum L.) and sandalwood (Santalum album L.). Optimization of the formulations was made by evaluating its biological activity through in vitro assay. Evaluation of physicochemical properties of the optimized formulation (UF-1) has been carried out by analysis of pH, flow properties and stability. Moreover, RP-HPLC (reverse phase - high performance liquid chromatography) and HPTLC (high performance thin layer chromatography) standardization of UF-1 was performed for its quantitative and qualitative analysis., Results: Ubtan formulations (UF-1to UF-4) showed free radical scavenging and ferric reducing potential. It may be due to its high phenolic and flavonoid content. Statistically, significant Pearson's correlation (r) was confirmed the positive correlation between phenolic content and SPF of the formulations. The tyrosinase inhibition study indicated that the formulations showed both diphenolase and monophenolase inhibitory activity. Among four formulations, UF-1 showed notable biological activity (p<0.05). The content of curcumin and ascorbic acid was found to be 1.6% and 2.1% w/w respectively in UF-1 through RP-HPLC estimation. Physiochemical properties of the UF-1 exhibited good flow rate and aqueous solubility. From the stability studies, it can be anticipated that the UF-1 was stable at 40°C for longer periods. Microbial load count and heavy metal content (lead-Pb, arsenic-As, mercury-Hg and cadmium-Cd) of the formulation was also within the permissible limit of a pharmacopeial standard., Conclusion: This scientific exploration helps to set the quality and safety standard of traditional cosmetic formulation, Ubtan and its further use as an herbal skin care product., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In the present study, the physiological effects on 32 humans exposed to experimental stress provoked by inhalation of the essential oils of East Indian sandalwood (Santalum album L.), Western Australian sandalwood (Santalum spicatum R.Br.) and lavender (Lavandula angustifolia MILL.) were investigated. During individual testing sessions, several saliva samples were collected, blood pressure was regularly measured and parameters of the autonomic nervous system (heart rate, skin conductance response) were continuously monitored. Salivary cortisol, as an endocrine stress indicator, was determined by time- resolved fluoroimmunoassay. Statistical analyses evidenced that the tested sandalwood essential oils significantly reduced systolic blood pressure, especially during the recreation phase. This finding corresponds with a distinct reduction of salivary cortisol levels during recreation in the Western Australian sandalwood oil compared with the control. In conclusion, the results demonstrate that essential oils can alleviate the physiological reactions to psychological stress and facilitate recovery after exposition to stress.

The present research deals with the multi-collection of the most important sesquiterpene alcohols belonging to sandalwood essential oil, as reported by the international regulations: (Z)-α-santalol, (Z)-α-trans bergamotol, (Z)-β-santalol, epi-(Z)-β-santalol, α-bisabolol, (Z)-lanceol, and (Z)-nuciferol. A versatile multidimensional preparative system, based on the hyphenation of liquid and gas chromatography techniques, was operated in the LC-GC-GC-prep or GC-GC-GC-prep configuration, depending on the concentration to be collected from the sample, without any hardware or software modification. The system was equipped with a silica LC column in combination with polyethylene glycol-poly(5% diphenyl/95% dimethylsiloxane)-medium polarity ionic liquid or β-cyclodextrin based GC stationary phases. The GC-GC-GC-prep configuration was exploited for the collection of four components, by using a conventional split/splitless injector, while the LC-GC-GC-prep approach was applied for three low abundant components (<5%), in order to increase the quantity collected within a single run, by the LC injection of a high sample amount. All target compounds, whose determination is hampered by the unavailability of commercial standards, were collected at milligram levels and with a high degree of purity (>87%)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with no major advancements in treatment over the past 40 years. The current study explores the biological effects of East Indian sandalwood oil (EISO) and its two major constituents, α- and β-santalol, against a variety of HNSCC lines. All three agents exhibited cytotoxic effects and caused accumulation of cells in the G2/M phases of the cell cycle. Additionally, treatment with these agents caused formation of multipolar mitotic spindles similar to those observed upon treatment of cells with compounds that affect microtubule polymerization. Indeed, the santalols, as well as EISO, inhibited the polymerization of purified tubulin, indicating for the first time that these compounds have the ability to directly bind to tubulin and affect microtubule formation. Modeling studies suggest that the santalols can weakly bind to the colchicine site on tubulin, and topical administration of EISO to a HNSCC xenograft inhibited tumor growth with no observed toxicities. Therefore, santalols can directly interact with tubulin to inhibit the polymerization of microtubules, similarly to established classes of chemotherapeutic agents, albeit with greatly reduced potency that is not associated with the classic toxicity associated with most other compounds that interact directly with tubulin.

With the advances in nanoscience and nanotechnology the interest of researchers has expanded to interdisciplinary domain like bio-medical applications. Among such domains, one of the most important areas explored meticulously is the development of promising solutions in diabetes therapeutics. The disease associated with metabolic disorder, is one of the major challenges, due to its ever-increasing number of patients. The adverse effects of the synthetic enzymes like α-amylase and α-glucosidase inhibitors have invited many scientists to develop promising contender with minimal side-effects. On the other hand, Zinc has strong role in insulin synthesis, storage and secretion and thus its deficiency can be related to diabetes. In this context we have explored natural extract of Red Sandalwood (RSW) as a potent anti-diabetic agent, in conjugation with ZnO nanoparticles. ZnO nanoparticles have been synthesized via soft chemistry routes and duly characterized for their phase formation with the help of X-ray diffraction technique and Field-Emission Scanning Electron Microscopy. These monodispersed nanoparticles, -20 nm in size, were further conjugated to RSW extract. The conjugation chemistry was studied via Fourier transform infrared spectroscopy, UV-visible spectroscopy. Extract loading percentage was found from thermo-gravimetric analysis. 65% of the RSW extract was found conjugated to the ZnO nanoparticles. The anti-diabetic activity was assessed with the help of like α-amylase and α-glucosidase inhibition assay with murine pancreatic and small intestinal extracts. It was observed that the conjugated ZnO-RSW nanoparticles showed excellent activity against the crude murine pancreatic glucosidase as compared to the individual ZnO nanoparticles and the RSW extract. The ZnO-RSW conjugate showed 61.93% of inhibition while the bare ZnO nanoparticles and RSW showed 21.48% and 5.90% respectively.

Effective management of tumorigenesis requires development of better anticancer agents with greater efficacy and fewer side-effects. Natural products are important sources for the development of chemotherapeutic agents and almost 60% of anticancer drugs are of natural origin. α-Santlol, a sesquiterpene isolated from Sandalwood, is known for a variety of therapeutic properties including anti-inflammatory, anti-oxidant, anti-viral and anti-bacterial activities. Cell line and animal studies reported chemopreventive effects of sandalwood oil and α-santalol without causing toxic side-effects. Our laboratory identified its anticancer effects in chemically-induced skin carcinogenesis in CD-1 and SENCAR mice, ultraviolet-B-induced skin carcinogenesis in SKH-1 mice and in vitro models of melanoma, non-melanoma, breast and prostate cancer. Its ability to induce cell-cycle arrest and apoptosis in cancer cells is its most reported anticancer mechanism of action. The present review discusses studies that support the anticancer effect and the mode of action of sandalwood oil and α-santalol in carcinogenesis., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The fragrant heartwood oil of West Australian sandalwood (Santalum spicatum) contains a mixture of sesquiterpene olefins and alcohols, including variable levels of the valuable sesquiterpene alcohols, α- and β-santalol, and often high levels of E,E-farnesol. Transcriptome analysis revealed sequences for a nearly complete set of genes of the sesquiterpenoid biosynthetic pathway in this commercially valuable sandalwood species. Transcriptome sequences were produced from heartwood xylem tissue of a farnesol-rich individual tree. From the assembly of 12,537 contigs, seven different terpene synthases (TPSs), several cytochromes P450, and allylic phosphatases were identified, as well as transcripts of the mevalonic acid and methylerythritol phosphate pathways. Five of the S. spicatum TPS sequences were previously unknown. The full-length cDNA of SspiTPS4 was cloned and the enzyme functionally characterized as a multi-product sesquisabinene B synthase, which complements previous characterization of santalene and bisabolol synthases in S. spicatum. While SspiTPS4 and previously cloned sandalwood TPSs do not explain the prevalence of E,E-farnesol in S. spicatum, the genes identified in this and previous work can form a basis for future studies on natural variation of sandalwood terpenoid oil profiles., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The sedative activity of eight aromatic natural medicines that are traditionally used in Japanese scent sachets was examined using an open field test with mice. Galangal (Kaempferia galanga), patchouli (Pogostemon cablin), sandalwood (Santalum album), spikenard (Nardostachys chinensis), cinnamon (Cinnamomum cassia), clove (Syzygium aromaticum), star anise (Illicium verum), and borneol (Dryobalanops aromatica) distilled oils were used. These natural medicines have various pharmacological effects. For example, galangal has insecticidal activity and clove extracts possess strong total antioxidant activity. Aromatherapy, a well-known complementary medicine system that uses inhalation, has recently attracted much attention. The sedative activity of inhaled aromatic compounds or essential oils has been examined by measuring the spontaneous motor activity of mice in an open field test. The galangal, patchouli, sandalwood, spikenard, and borneol oils showed significant sedative effects. The effect was stronger for a mixture of the five oils than for any of the single oils. This suggests that the oil mixture may have synergistic activity. Sedative activity was not observed when inactive oils (cinnamon, clove, and star anise) were added to the mixture of the five active oils., (Georg Thieme Verlag KG Stuttgart · New York.)

A series of eleven β-santalol analogs, including nine new derivatives, was prepared by semisynthesis from natural (-)-(Z)-β-santalol and studied by gas chromatography-olfactometry (GC-O) to characterize their olfactory properties and potencies. These compounds and 45 others selected in the literature were used to build three olfactophores by molecular modelling. Three models were obtained that gather structural and physicochemical constraints that will be useful for further design of new sandalwood odorants., (Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.)

Skin contains receptors for various environmental factors. In this issue of the Journal, Busse et al. cloned a new olfactory receptor, OR2AT4, in keratinocytes. They show that the activation of OR2AT4 induces phosphorylation of extracellular signal-regulated kinases and p38 mitogen-activated protein kinases, and that it accelerates wound healing. OR2AT4 may be a promising candidate as a target in clinical drug development.

As the outermost barrier of the body, the skin is exposed to multiple environmental factors, including temperature, humidity, mechanical stress, and chemical stimuli such as odorants that are often used in cosmetic articles. Keratinocytes, the major cell type of the epidermal layer, express a variety of different sensory receptors that enable them to react to various environmental stimuli and process information in the skin. Here we report the identification of a novel type of chemoreceptors in human keratinocytes, the olfactory receptors (ORs). We cloned and functionally expressed the cutaneous OR, OR2AT4, and identified Sandalore, a synthetic sandalwood odorant, as an agonist of this receptor. Sandalore induces strong Ca(2+) signals in cultured human keratinocytes, which are mediated by OR2AT4, as demonstrated by receptor knockdown experiments using RNA interference. The activation of OR2AT4 induces a cAMP-dependent pathway and phosphorylation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Moreover, the long-term stimulation of keratinocytes with Sandalore positively affected cell proliferation and migration, and regeneration of keratinocyte monolayers in an in vitro wound scratch assay. These findings combined with our studies on human skin organ cultures strongly indicate that the OR 2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes.

Four commercial qualities of Hawaiian sandalwood oil produced from wood of Santalum paniculatum originating from the island of Hawaii ("The Big Island") were analyzed using GC and GC-MS. Main constituents of the oils were (Z)-α-santalol (34.5-40.4%) and (Z)-β-santalol (11.0-16.2%). An odor evaluation of the oils was carried out against East Indian sandalwood oil. In addition, the chemical composition of Hawaiian sandalwood oil was compared with four different Santalum species originating from East India, New Caledonia, Eastern Polynesia and Australia, respectively.

Ethnopharmacological Relevance: Santalum album L., namely Sandalwood, honored as "Green Gold", is a traditional Chinese herb which has the effects of anti-diarrhoeal and antibacterial activity. But there is limit scientific study on its activity and mechanism in gastrointestinal disorders., Materials and Methods: in vivo, after intragastric administration, the methanol extract of Sandalwood (SE) (200, 400 and 800 mg/kg) were studied in castor oil-induced diarrhoea mice. By the test of small intestinal hyperfunction induced by neostigmine, SE was studied on gastrointestinal transit including gastric emptying and small intestinal motility. Meanwhile, in vitro, the effects of SE (0.02, 0.05, 0.1, 0.2, 0.3, 0.4 mg/mL) on the isolated tissue preparations of rat jejunum were also investigated. The rat jejunum strips were pre-contracted with acetylcholine (Ach; 10(-6)M), 5-hydroxytryptamine (5-HT, 200 μM) or potassium chloride (KCl; 60 mM) and tested in the presence of SE. In addition, the possible myogenic effect was analyzed in the pretreatment of the jejunum preparations with SE or verapamil in Ca(2+)-free high-K(+) (60 mM) solution containing EDTA., Results: At doses of 200, 400 and 800 mg/kg, SE showed significant anti-diarrhoeal activity against castor oil-induced diarrhoea as compared with the control. At the same doses, it also inhibited the gastric emptying and small intestinal motility in the mice of which small intestinal hyperfunction induced by neostigmine. It caused inhibitory effects on the spontaneous contraction of rat-isolated jejunum in dose-dependent manner ranging from 0.02 to 0.4 mg/mL, and it also relaxed the Ach-induced, 5-HT-induced and K(+)-induced contractions. SE shifted the Ca(2+) concentration-response curves to right, similar to that caused by verapamil (0.025 mM)., Conclusions: These findings indicated that SE played a spasmolytic role in gastrointestinal motility which was probably mediated through inhibition of muscarinic receptors, 5-HT receptors and calcium influx. All these results provide pharmacological basis for its clinical use in gastrointestinal tract., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme-linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co-cultured human dermal fibroblasts and neo-epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α-santalol and β-santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α-santalol and β-santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α-santalol and β-santalol also suppressed lipopolysaccharide-induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co-cultures. The ability of SOs to mimic ibuprofen non-steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects., (Copyright © 2013 John Wiley & Sons, Ltd.)

Small cyclic peptides exhibiting potent biological activity have great potential for anticancer therapy. An antiproliferative cyclic octapeptide, cyclosaplin was purified from somatic seedlings of Santalum album L. (sandalwood) using gel filtration and RP-HPLC separation process. The molecular mass of purified peptide was found to be 858 Da and the sequence was determined by MALDI-ToF-PSD-MS as 'RLGDGCTR' (cyclic). The cytotoxic activity of the peptide was tested against human breast cancer (MDA-MB-231) cell line in a dose and time-dependent manner. The purified peptide exhibited significant antiproliferative activity with an IC50 2.06 μg/mL. In a mechanistic approach, apoptosis was observed in differential microscopic studies for peptide treated MDA-MB-231 cells, which was further confirmed by mitochondrial membrane potential, DNA fragmentation assay, cell cycle analysis and caspase 3 activities. The modeling and docking experiments revealed strong affinity (kcal/mol) of peptide toward EGFR and procaspase 3. The co-localization studies revealed that the peptide sensitizes MDA-MB-231 cells by possibly binding to EGFR and induces apoptosis. This unique cyclic octapeptide revealed to be a favorable candidate for development of anticancer agents., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A rare type of sesquiterpene with a spiro bicyclic system (1) and seven new (2-8) and four known (9-12) β-santalol derivatives were isolated from the heartwood of Santalum album (Santalaceae). The structures of these new compounds were determined by analysis of extensive spectroscopic data. The isolated compounds and derivatives were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, HSC-2 and HSC-4 human oral squamous cell carcinoma cell lines, and TIG-3 normal human diploid fibroblasts. cis-β-Santalol (9) and β-santaldiol (10) induced apoptotic cell death in HL-60 cells.

The human estrogen receptor alpha (ERα) mediates the proliferative action of hormones in breast cancer cells by regulating the expression of target genes to control cellular functions. Current methodologies do not permit a real-time assessment of these processes in living cells. We overcome this limitation using electrical cell-substrate impedance sensing for measuring ERα-regulated signaling processes indicative of the onset of cell proliferation to target them for compound screenings. We report that hormone like odorants regulate, similarly as natural estrogen, ERα-mediated gene expression involved in mitogenic and developmental processes in MCF7 breast cancer cells. An odorant concentration-dependent switch in cell responses was detectable already 10-15 h post-stimulation, providing rapid quantification of hormonal activity before cell division occurred. Though ERα exhibits complex regulatory roles our non-invasive approach captures its activity for accelerated screenings of compounds promoting breast cancer cell proliferation expanding the analysis of ERα signaling networks., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Dactylogyrus spp. and Gyrodactylus spp. are helminth ectoparasites that are a significant threat to the aquaculture industry. Existing treatments could cause the threats of anthelmintic resistance, risk of residues, environmental contamination, and toxicity to fish. Importantly, there is no report on a treatment against these two parasites. This study explored the possibility of using the extracts of Santalum album to treat Dactylogyrus sp. and Gyrodactylus sp. infections in goldfish. Results showed that among the four extracts (chloroform, methanol, ethyl acetate, and water) of S. album, the chloroform extract is the most effective and 40 mg/L is a safe and the lowest effective dosage. In addition, we found that Gyrodactylus elegans is more sensitive than Dactylogyrus intermedius when exposed to the extract of the medicinal plant. Finally, it is substantiated that bath treatment with long duration and multiple administrations could eliminate a greater proportion of monogenean infections. These findings show the potential for the development of effective and safe therapy to treat Dactylogyrus sp. and Gyrodactylus sp. infections of fishes.

Alpha-Santalol is a sesquiterpene that is a major constituent of sandalwood (Santalum album L.), and is responsible for its distinctive woody odor. We replaced the polycyclic moiety and hydroxyl group of alpha-santalol with other moieties, and we compared the odors of the E/Z-isomers and their saturated analogues. Our previous study of the structure-odor relationships of alpha-santalols bearing hydroxyl, formyl, formyloxy, and acetoxy functional groups showed there was a similarity in odor between the Z-isomer and its saturated analogue. We synthesized alpha-santalols with a benzyl group in place of the hydroxyl group, because many benzyl compounds have strong characteristic odors. We found similar odors for the E-isomer and its saturated analogue. In contrast, the odors of the alpha-santalol derivatives with a hydroxyl, formyl, formyloxy, or acetoxy group were different. We also replaced the bulky polycyclic moiety with a linear alkyl chain. The polycyclic moiety was the most important structural factor in the characteristic sandalwood odor. The synthesis of derivatives and the evaluation of their odor allowed us to identify the key structural factors in the odor of alpha-santalol.

An LC-MS/MS method was developed for the simultaneous determination of vitexin and isovitexin in rat plasma, using puerarin as the internal standard (IS). Plasma samples extracted with protein precipitation procedure were separated on a Diamonsil® C(18) column (150 × 4.6 mm, 5 µm) with a mobile phase composed of methanol and 0.1% formic acid (45:55, v/v). The detection was accomplished by multiple reaction monitoring mode in positive electrospray ionization source. The optimized mass transition ion-pairs for quantitation were m/z 431.2 → 311.1 for vitexin and isovitexin, and m/z 415.1 → 295.1 for IS. The total run time was 7.5 min for each injection. The calibration curves were linear (r(2) > 0.99) over the investigated concentration range (2.00-2000 ng/mL) and the lower limits of quantification were 2.00 ng/mL in rat plasma sample. The intra- and inter-day relative standard deviations were no more than 14.9% and the relative errors were within the range of -3.2-2.1%. The extraction recoveries for both compounds were between 89.3 and 97.3%. The robust LC-MS/MS method was further applied in the pharmacokinetic study in Sprague-Dawley rats after oral administration of Santalum album L. leaves extract at a dose of 116 mg/kg., (Copyright © 2012 John Wiley & Sons, Ltd.)

The aim of the present study was to investigate the effect of sandalwood seed oil on fatty acid (FA) profiles and inflammatory factors in rats. Fifty male Sprague-Dawley rats were randomly divided into five different dietary groups: 10 % soybean oil (SO), 10 % olive oil (OO), 10 % safflower oil (SFO), 10 % linseed oil (LSO) and 8 % sandalwood seed oil blended with 2 % SO (SWSO) for 8 weeks. The SWSO group had a higher total n-3 polyunsaturated fatty acids (PUFA) levels but lower n-6:n-3 PUFA ratios in both adipose tissue and liver than those in the SO, OO and SFO groups (p < 0.05). Although the SWSO group had a much lower 18:3n-3 level (4.51 %) in their dietary lipids than the LSO group (58.88 %), the levels of docosahexaenoic acid (DHA: 22:6n-3) in liver lipids and phospholipids of the SWSO group (7.52 and 11.77 %) were comparable to those of the LSO group (7.07 and 13.16 %). Ximenynic acid, a predominant acetylenic FA in sandalwood seed oil, was found to be highly incorporated into adipose tissue (13.73 %), but relatively lower in liver (0.51 %) in the SWSO group. The levels of prostaglandin F(2α), prostaglandin E₂, thromboxane B₂, leukotriene B₄, tumor necrosis factor-α and interleukin-1β in both liver and plasma were positively correlated with the n-6:n-3 ratios, suggesting that increased n-6 PUFA appear to increase the formation of pro-inflammatory cytokines, whereas n-3 PUFA exhibit anti-inflammatory activity. The present results suggest that sandalwood seed oil could increase tissue levels of n-3 PUFA, DHA and reduce the n-6:n-3 ratio, and may increase the anti-inflammatory activity in rats.

Unlabelled: Sandalwood oil has been found in numerous therapeutic applications in traditional medicines such as Chinese traditional medicine and Ayurveda. However, there are no comparative accounts available in the literature that focused on in vitro and in vivo tree sample-derived extracts. Combined dichloromethane and methanol extracts were obtained from in vitro samples, that is, callus, somatic embryo and seedlings, and in vivo from leaves of non-oil-yielding young and oil-yielding matured trees. Phytochemical evaluation of the extracts reveals that the tree is rich in terpenoids, saponin, phenolics and tannins. The antibacterial properties of the five extracts were compared with sandalwood oil by screening against nine Gram-negative and five Gram-positive bacterial strains by disc diffusion, agar spot and TLC bioautography methods. Minimum inhibitory concentration (MIC) for sandalwood oil was determined to be in the range of 0·078-5 μg ml(-1) for most of the test micro-organisms screened. Bioautography results indicated the presence of potential antimicrobial constituents in somatic embryo extracts and sandalwood oil. Among the extracts screened, the somatic embryo extracts showed the strongest antibacterial activity comparable only with sandalwood oil and matured tree leaves' extract. The findings presented here also suggest that apart from sandalwood oil, other parts of this tree across developmental stages are also enriched with antibacterial principles., Significance and Impact of Study: This study constitutes the first systematic investigation on phytochemical composition and antimicrobial efficacy of sandalwood tree across in vitro and in vivo developmental stages screened against thirteen bacterial strains by four methods. Using a battery of antimicrobial assay techniques, it is possible to follow the differential bioactive metabolic richness of plant parts, to decipher, for example comparable efficacy of somatic embryo extracts and sandalwood oil., (© 2012 The Society for Applied Microbiology.)

The major sesquiterpene constituents of East-Indian sandalwood oil (Z)-α- and (Z)-β-santalols have shown to be responsible for most of the biological activities and organoleptic properties of sandalwood oil. The work reported here describes the strategic use of medium pressure liquid chromatography (MPLC) for the separation of both α- and β-santalenes and (Z)-α- and (Z)-β-santalols. Silver nitrate impregnated silica gel was used as the stationary phase in MPLC for quantitative separation of α- and β-santalenes and (Z)-α- and (Z)-β-santalols with mobile phases hexane and dichloromethane, respectively. The purities of α-santalene and (Z)-α-santalol obtained were >96%; however, β-santalene and (Z)-β-santalol were obtained with their respective inseparable epi-isomers. Limits of quantification (LoQ) relative to the FID detector were measured for important sesquiterpene alcohols of heartwood oil of S. album using serial dilutions of the standard stock solutions and demonstrated that the quality of the commercial sandalwood oil can be assessed for the content of individual sesquiterpene alcohols regulated by Australian Standard (AS2112-2003), International Organization for Standardization ISO 3518:2002 (E) and European Union (E. U.).

A bioassay-guided fractionation of the heartwood of Santalum album led to the isolation of seven α-santalol derivatives including (9S,10E)-9-hydroxy-α-santalal, (10R,11S)-10,11-dihydroxy-α-santalol, (9E)-11,13-dihydroxy-α-santalol, and (10E)-12-hydroxy-α-santalic acid. Their structures were determined on the basis of results of spectroscopic analysis, including two-dimensional (2D) NMR spectroscopic data. The isolated compounds and derivatives were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and TIG-3 normal human diploid fibroblasts. Of these (9S,10E)-9-hydroxy-α-santalal, exhibited tumor-selective cytotoxicity. The apoptosis induction properties of sesquiterpenes with cytotoxic potency in HL-60 cells are also described., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Abstract. The anti-plasmodial activity of 47 essential oils and 10 of their constituents were screened for in vitro activity against Plasmodium falciparum. Five of these essential oils (sandalwood, caraway, monarda, nutmeg, and Thujopsis dolabrata var. hondai) and 2 constituents (thymoquinone and hinokitiol) were found to be active against P. falciparum in vitro, with 50% inhibitory concentration (IC50) values equal to or less than 1.0 microg/ml. Furthermore, in vivo analysis using a rodent model confirmed the anti-plasmodial potential of subcutaneously administered sandalwood oil, and percutaneously administered hinokitiol and caraway oil against rodent P. berghei. Notably, these oils showed no efficacy when administered orally, intraperitoneally or intravenously. Caraway oil and hinokitiol dissolved in carrier oil, applied to the skin of hairless mice caused high levels in the blood, with concentrations exceeding their IC50 values.

Context: Santalum album Linn (Santalaceae), commonly known as Sandalwood is used traditionally for its antihyperlipidemic and diuretic activity., Objective: This study investigated the antihyperglycemic and antihyperlipidemic effect of long-term oral administration of the Santalum album pet ether fraction in streptozotocin-induced diabetic rats., Materials and Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin at 70 mg/kg body weight. Rats were treated with Santalum album pet ether fraction orally at a dose of 10 µg/kg body weight twice daily for 60 days. Metformin (30 mg/kg body weight) was used as positive control. Lipid profile and glycated hemoglobin were estimated. HPLC profiling of Santalum album pet ether fraction was carried out., Results and Discussion: Treatment of diabetic rats for 60 days demonstrated reduction in blood glucose level by 140 mg/dl. Metformin treated group showed a decrease in blood glucose by 70 mg/dl, as against an increase in diabetic control group by 125 mg/dl. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 22, 31 and 44%, respectively, in treated diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) increased by 46%. In case of metformin, the values were 11, 29 and 15% respectively, while HDL increased by 7%. Significant improvement in atherogenic index from 267 to 139% was observed in treated rats., Conclusion: Santalum album pet ether fraction has potential antihyperlipidemic activity that can help in overcoming insulin resistance.

The anti-influenza A/HK (H3N2) virus activity of β-santalol was evaluated in MDCK cells and investigated the effect of β-santalol on synthesis of viral mRNAs. β-Santalol was investigated for its antiviral activity against influenza A/HK (H3N2) virus using a cytopathic effect (CPE) reduction method. β-Santalol exhibited anti-influenza A/HK (H3N2) virus activity of 86% with no cytotoxicity at the concentration of 100 μg/ml reducing the formation of a visible CPE. Oseltamivir also showed moderate antiviral activity of about 83% against influenza A/HK (H3N2) virus at the concentration of 100 μg/ml. Furthermore, the mechanism of anti-influenza virus action in the inhibition of viral mRNA synthesis was analyzed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), and the data indicated an inhibitory effect in late viral RNA synthesis compared with oseltamivir in the presence of 100 μg/ml of β-santalol. β-Santalol should be further studied for therapeutic and prophylactic potential especially for influenza epidemics and pandemics., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

The chemical composition of volatile compounds from pericarp oils of Indian sandalwood, Santalum album L., isolated by hydrodistillation and solvent extraction, were analyzed by GC and GC-MS. The pericarps yielded 2.6 and 5.0% volatile oil by hydrodistillation and n-hexane extraction, and they were colorless and yellow in color, respectively. A total of 66 volatile components were detected. The most prominent compounds were palmitic and oleic acids, representing about 40-70% of the total oil. Many fragrant constituents and biologically active components, such as alpha- and beta-santalol, cedrol, esters, aldehydes, phytosterols, and squalene were present in the pericarp oils. This is the first report of the volatile composition of the pericarps of any Santalum species.

Objective: To study the flavonoids from the leaves of Santalum album., Method: The sample was extracted with 70% ethanol by continuous thermal reflux. The extraction was separated and purified by column chromatography over macroporous adsorption resin, polyamide and sephadexlh-20. Their structures were identified by detailed spectroscopic analysis., Result: Eight flavonoids were isolated and identified as vicenin-2 (1), vitexin (2), isovitexin (3), orientin (4), isoorientin (5). chrysin-8-C-beta-D-glucopyranoside (6), chrysin-6-C-beta-D-glucopyranoside (7), and isorhamnetin (8)., Conclusion: All compounds were isolated from this plant for the first time.

The production and trade of Indian sandalwood oil is strictly regulated, due to the impoverishment of the plantations; for such a reason, Australian sandalwood oil has been evaluated as a possible substitute of the Indian type. International directives report, for both the genuine essential oils, specific ranges for the sesquiterpene alcohols (santalols). In the present investigation, a multidimensional gas chromatographic system (MDGC), equipped with simultaneous flame ionization and mass spectrometric detection (FID/MS), has been successfully applied to the analysis of a series of sandalwood oils of different origin. A detailed description of the system utilized is reported. Three santalol isomers, (Z)-α-trans-bergamotol, (E,E)-farnesol, (Z)-nuciferol, epi-α-bisabolol and (Z)-lanceol have been quantified. LoD (MS) and LoQ (FID) values were determined for (E,E)-farnesol, used as representative of the oxygenated sesquiterpenic group, showing levels equal to 0.002% and 0.003%, respectively. A great advantage of the instrumental configuration herein discussed, is represented by the fact that identification and quantitation of target analytes are carried out in one step, without the need to perform two separate analyses., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Alpha-santalol, a naturally occurring terpenoid, has been shown to have chemopreventive effects on both 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O- tetradecanoylphorbol-13-acetate (TPA)-promoted skin cancer development in CD-1 and SENCAR mice, and UVB-induced skin cancer developments in SKH-1 hairless mice in a concentration-dependent manner. Studies have demonstrated that α-santalol could be effective against skin carcinogenesis through both induction of apoptosis via caspase activation together with dissipation of mitochondria membrane potential and cytochrome c release in A431 cells, and inhibition of cell growth via induction of G2/M phase arrest in both A431 cells and melanoma UACC-62 cells by altering multiple cell cycle regulatory proteins and complexes. This review summarizes the chemopreventive effects and molecular mechanisms of α-santalol on skin cancer development in both animal models and skin cancer cell lines.