Sandalwood Oil Research Articles

419 Inhibition of Phosphodiesterase 4 (PDE 4) by East Indian Sandalwood Oil (EISO): A new therapeutic option for inflammatory skin diseases

419 Inhibition of Phosphodiesterase 4 (PDE 4) by East Indian Sandalwood Oil (EISO): A new therapeutic option for inflammatory skin diseases

LC-MS-based Screening of East Indian Sandalwood Oil for Mycobacterium tuberculosis Shikimate Kinase and Plasmodium falciparum Thioredoxin Reductase Inhibitory Activities

M. tuberculosis shikimate kinase ( MtSK) and P. falciparum thioredoxin reductase ( PfTrxR) represent promising drug targets in tuberculosis and malaria therapy respectively. East Indian Sandalwood oil (EISO) has many reported therapeutic benefits including antibacterial and antiplasmodial effects. The aim of this study was to screen EISO for MtSK and PfTrxR inhibition as potential mechanisms of antimycobacterial and antiplasmodial activities. Liquid chromatography-mass spectrometry (LC-MS) functional assays were used to assess MtSK and PfTrxR inhibition. In this study, EISO displayed antitubercular activity against M. tuberculosis H37Rv at MIC value of 0.002% v/v. Subsequently preliminary screening of the MtSK inhibition by EISO showed an IC50 value of 0.015% v/v. Additionally, EISO presented 90% inhibition of PfTrxR at 0.01% v/v suggesting a potential mechanism of action for reported antimalarial activity.

Antifungal and Ichthyotoxic Sesquiterpenoids from Santalum album Heartwood.

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.

VARIATION OF CHEMICAL COMPOUNDS OF SANDALWOOD OIL FROM VARIOUS PROVENANCES IN INDONESIA

The quality of sandalwood (Santalum album Linn) oil primarily depends on the compound of two major sesquiterpenes (α-santalol and β-santalol). The aim of this research was to identify variation of chemical compounds of sandalwood oil from various provenances. Fifty four samples from 8 provenances and one land race taken from 13th years old sandalwood planted at Gunungkidul, Yogyakarta Indonesia. Sandalwood powder were obtained by drilling tree at 10 cm above the ground horizontally. The samples were extracted with n-hexane solvent. Identification of chemical compounds of this essential oils were conducted by gas chromatography mass spectrometry analysis (GCMS). The GCMS investigation of sandalwood oils showed that variation compounds both among individual within provenance and between provenances were found in 11 individual from 6 provenances. Compounds such as sesquiterpene, monoterpenes, and others, were found in variying amount. The results showed that α-santalol (32.38-78.29%), β-santalol (5.45%-37.83%) were the major compounds with varying quantities of compounds range of epi-β-santalol (5.97-17.16%), P-Menth-2-En-9-OL-Trans (2.87%-8.53%), and α-sinensal (3.83-9.39%).

Sandalwood Oil and Turmeric-Based Cream Prevents Ionizing Radiation-Induced Dermatitis in Breast Cancer Patients: Clinical Study.

Background: The primary objective of this study was to ascertain the benefit of Vicco turmeric Ayurvedic cream (VTC; Vicco Laboratories, Mumbai, India) sandalwood oil and turmeric-based cream in preventing radiodermatitis in women undergoing curative radiotherapy for their breast cancer. Methods and Materials: The study was an investigator-blinded randomized study with Johnsons Baby Oil (JBO; Johnson & Johnson Ltd., Baddi, India) as a comparator, administered daily from the start of radiation therapy for 5 weeks in women receiving breast radiation therapy, 50 Gy in 2 Gy fractions daily for 5 weeks. The endpoints were to ascertain the delay in the appearance and the degree of severity of dermatitis throughout the study period in accordance to the Therapy Oncology Group (RTOG) score. Results: The results indicated that the topical application of VTC delayed and mitigated the radiodermatitis. When compared to the Johnson’s Baby Oil, a significant decrease (p = 0.025) in the incidence of grade 1 was seen at week two, and also in grade 2 and 3 at week 3 (p = 0.003) and week 4 (p = 0.02), respectively, in the VTC cohort. A concomitant decrease in the average severity was also observed at week 2 (p = 0.02), week 3 (p = 0.05) and week 4 (p = 0.03). Conclusions: The results indicate that VTC cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. The result of this study indicates the beneficial effects. Double blind randomized control studies are required to further confirm the beneficial effects of VTC in mitigating radiodermatitis is people undergoing radiation treatment for their cancer.

VARIASI KANDUNGAN KIMIA MINYAK CENDANA (Santalum album Linn) DARI BERBAGAI PROVENANS DI INDONESIA

The quality of sandalwood (Santalum album Linn) oil primarily depends on the compound of two major sesquiterpenes (α-santalol and β-santalol). The aim of this research was to identify variation of chemical compounds of sandalwood oil from various provenances. Fifty four samples from 8 provenances and one land race taken from 13th years old sandalwood planted at Gunungkidul, Yogyakarta Indonesia. Sandalwood powder were obtained by drilling tree at 10 cm above the ground horizontally. The samples were extracted with n-hexane solvent. Identification of chemical compounds of this essential oils were conducted by gas chromatography mass spectrometry analysis (GCMS). The GCMS investigation of sandalwood oils showed that variation compounds both among individual within provenance and between provenances were found in 11 individual from 6 provenances. Compounds such as sesquiterpene, monoterpenes, and others, were found in variying amount. The results showed that α-santalol (32.38-78.29%), β-santalol (5.45%-37.83%) were the major compounds with varying quantities of compounds range of epi-β-santalol (5.97-17.16%), P-Menth-2-En-9-OL-Trans (2.87%-8.53%), and α-sinensal (3.83-9.39%).

Multiple strategies for increasing yields of essential oil and obtaining sandalwood terpenoids by biotechnological methods in sandalwood

Sandalwood essential oil or terpenoids are highly valued. This review summarizes several methods for increasing yields of sandalwood essential oil or terpenoids and the molecular mechanisms of sandalwood terpene biosynthesis. Sandalwood is highly valued for its aromatic heartwood and essential oil, which is not only broadly applied in the fragrance industry, but also has various biological activities: anti-cancer, anti-tumor, anti-viral, anti-diarrhoeal, etc. The main contributors of sandalwood essential oil fragrance are (Z)-α-santalol and (Z)-β-santalol. Global sandalwood resources are often in short supply because of slow growth, habitat destruction, illegal use of natural stocks, over exploitation, plant disease and insect pests. Thus, various methods are used to overcome these shortcomings to obtain more sandalwood essential oil or terpenoids. At first, an understanding of the molecular mechanism of sandalwood terpenoid biosynthesis is urgently required. Here, we review the mechanism of sandalwood terpenoid biosynthesis and multiple strategies for increasing the yield of essential oil and obtaining sandalwood terpenoids by biotechnological methods. Three major topics are discussed: (1) the metabolic pathway of sandalwood terpenoid biosynthesis, (2) how to obtain sandalwood terpenoids or essential oil by chemical synthesis, the application of elicitors and the plant cell culture, and (3) heterologous synthesis of sandalwood terpenoids.

East Indian Sandalwood Oil (EISO) Alleviates Inflammatory and Proliferative Pathologies of Psoriasis.

Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2–3% of the world’s population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1β. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized in vitro psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies.

Kinetic studies on extraction of essential oil from sandalwood (Santalum album) by microwave air-hydrodistillation method

Essential oil from sandalwood is commonly obtained by conventional extraction methods which requires great energy, significant amount of solvents, and quite a long process time. Therefore, the use of new ‘green method’ for extracting essential oil with minimum/low energy, solvents, and time needs to be considered. One extraction method that has been successfully developed is microwave hydrodistillation method. This research employs a method developed from microwave hydrodistillation, that is microwave air-hydrodistillation for optimizing the extraction of essential oil. The purpose of this study was to examine the effect of the presence and absence of additional air flow to the microwavehydrodistillation method. The material used in this study includes sandalwood powder. The extractions by microwave hydrodistillation and microwave air-hydrodistillation methods were done on the power of 600W; the ratio of the raw material to be extracted and the solvent was 0.05gmL−1 and the extraction time was 120min. In the extraction by microwave air-hydrodistillation, the rates of air flow used were 0.1, 0.5, 1.5, 3.0, and 5.0L/min. The results of the research show that the extraction of sandalwood oil by microwave air-hydrodistillation is faster and produces higher yields compared to the extraction by microwave hydrodistillation method. Based on kinetics modeling that has been done, it can be said that the second-order kinetic model more can represent well the experimental results of sandalwood oil extraction by microwave hydrodistillation and microwave air-hydrodistillation methods when compared with the first-order kinetic model. The testing of the physical properties of the sandalwood oil indicates that essential oil obtained by microwave hydrodistillation and microwave air-hydrodistillation has the same quality (refractive index and specific gravity). Further, the testing of the chemical properties of the sandalwood oil shows that essential oil obtained by microwave air-hydrodistillation has better quality (flavor) compared to the oil obtained by microwave hydrodistillation.

Santalum molecular biology: molecular markers for genetic diversity, phylogenetics and taxonomy, and genetic transformation

Species of the Santalum genus are well known for their fragrant hardwood, which has great value in medicinal, pharmaceutical and cosmetic industries. Sandalwood oil is derived from the heartwood of Santalum sp. and contains α-, β- and epi-β-santalols, which are responsible for its pleasant fragrance. Oil content can vary from species to species. Pressure on natural populations due to habitat loss, legal and illegal harvesting and disease is increasing. This paper highlights the development of molecular markers for the refinement of phylogenetic studies, identification of various Santalum and adulterant species, assessment of genetic diversity, genetic differentiation, clonality and management units within species, and for marker-assisted breeding. The identification of quantitative trait loci for sandal spike disease and for other traits such as specific rare secondary metabolites in the essential oil and related to its fragrance, would also benefit from molecular advances. RNA sequence analyses have already identified changes in gene expression and metabolic pathways in developing Santalum album L. haustoria.

Topical Sandalwood Oil for Common Warts.

The purpose of this study was to evaluate the effectiveness of sandalwood oil for cutaneous viral warts caused by human papillomavirus. Sandalwood oil was applied topically twice daily for 12 weeks to cutaneous warts on any area of the body. Data collected at each visit included measurement of wart size, photograph of the warts, and documentation of treatment compliance and any adverse reactions. Ten subjects were enrolled and received treatment. At the end of the study, 8 of 10 (80%) had complete resolution of all treated warts. The remaining 2 subjects had improvement rated as moderate (25% to >90%). There were no complaints of skin irritation, erythema, itching, peeling of skin or scarring, pain or discomfort, or other adverse events reported. Sandalwood oil appears to be effective in the painless treatment of cutaneous warts caused by human papillomavirus.

Essential Oils, Part VI: Sandalwood Oil, Ylang-Ylang Oil, and Jasmine Absolute.

In this article, some aspects of sandalwood oil, ylang-ylang oil, and jasmine absolute are discussed including their botanical origin, uses of the plants and the oils and absolute, chemical composition, contact allergy to and allergic contact dermatitis from these essential oils and absolute, and their causative allergenic ingredients.

A Pilot Study on the Physiological Effects of Three Essential Oils in Humans

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.

Sandalwood oil downregulates skin inflammation through 11β-HSD1 activation in keratinocytes

Sandalwood oil downregulates skin inflammation through 11β-HSD1 activation in keratinocytes

Sandalwood oil enhanced Epithelial-Mesenchymal Transition and promoted wound healing

Sandalwood oil enhanced Epithelial-Mesenchymal Transition and promoted wound healing

Abstract 4608: Survivin downregulation by α-santalol is not mediated through PI3K-Akt pathway in human breast cancer cells

Abstract α-Santalol, a terpenoid found in sandalwood oil, has been shown to inhibit cancer cell growth in vitro by inducing apoptosis. This study was performed to investigate the anticancer properties of α-santalol associated with the induction of apoptosis in cultured MCF-7 (estrogen receptor (ER) positive, and wild type p53) and MDA-MB-231 (ER-negative and mutant p53) breast cancer cells. Expression of major proteins examined in the study were determined using standard Western blot protocol and analyzed by LICOR-Odyssey infra-red scanner. Total protein levels of survivin were confirmed by survivin ELISA kit. Cell viability was assessed by trypan blue dye exclusion assay, and caspase-3 activity was determined by caspase-3 (active) ELISA kit. Treatment of breast cancer cells for 6 and 9 hour time intervals with α-santalol (20, 40 μM) resulted in statistically significant concentration-dependent downregulation of survivin. pAkt levels were found to be slightly upregulated despite the downregulation of survivin. Pharmacological inhibition of the PI3K-Akt pathway did not result in a synergistic/additive increase in cell death or caspase-3 activity caused by α-santalol. The study reveals that survivin downregulation by α-santalol in breast cancer cells is not mediated through the PI3K-Akt pathway. Citation Format: AJAY BOMMAREDDY, KARRYN CRISAMORE, SARAH FILLMAN, SARAH BROZENA, JAMES STEIGERWALT, TERRA LANDIS, ADAM L. VANWERT, CHANDRADHAR DWIVEDI. Survivin downregulation by α-santalol is not mediated through PI3K-Akt pathway in human breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4608.

Parasitic angiosperms as cultivated plants?

The knowledge about parasitic plants has increased in the latest years. Their importance as economic plants is generally considered low. Some of the species came into cultivation mainly as medicinal plants, fruit trees and some as vegetables. Only Olacaceae (1), Opiliaceae (1), Santalaceae (6), Viscaceae (1), Ximeniaceae (1) and Orobanchaceae (3) contain some cultivated species (number in brackets). Santalum spp. (root parasites) and Viscum album (stem parasite) are of greater importance for the production of sandalwood oil and an anti-cancer medicine, respectively. Their parasitic nature is well known to the growers. In other cases, the parasitic nature is not noted, especially in semiparasitic root species (Arjona, Anacolosa). New results are to be expected with holoparasitic root parasites (Cistanche, Orobanche).

Preliminary Study: Kinetics of Oil Extraction from Sandalwood by Microwave-assisted Hydrodistillation

Sandalwood and its oil, is one of the oldest known perfume materials and has a long history (more than 4000 years) of use as mentioned in Sanskrit manuscripts. Sandalwood oil plays an important role as an export commodity in many countries and its widely used in the food, perfumery and pharmaceuticals industries. The aim of this study is to know and verify the kinetics and mechanism of microwave-assisted hydrodistillation of sandalwood based on a second-order model. In this study, microwave-assisted hydrodistillation is used to extract essential oils from sandalwood. The extraction was carried out in ten extraction cycles of 15 min to 2.5 hours. The initial extraction rate, the extraction capacity and the second-order extraction rate constant were calculated using the model. Kinetics of oil extraction from sandalwood by microwave-assisted hydrodistillation proved that the extraction process was based on the second-order extraction model as the experimentally done in three different steps. The initial extraction rate, h, was 0.0232 g L-1 min-1, the extraction capacity, CS, was 0.6015 g L-1, the second-order extraction rate constant, k, was 0.0642 L g-1 min-1 and coefficient of determination, R2, was 0.9597.

Heartwood-specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)-santalol fragrance biosynthesis.

Tropical sandalwood (Santalum album) produces one of the world's most highly prized fragrances, which is extracted from mature heartwood. However, in some places such as southern India, natural populations of this slow-growing tree are threatened by over-exploitation. Sandalwood oil contains four major and fragrance-defining sesquiterpenols: (Z)-α-santalol, (Z)-β-santalol, (Z)-epi-β-santalol and (Z)-α-exo-bergamotol. The first committed step in their biosynthesis is catalyzed by a multi-product santalene/bergamotene synthase. Sandalwood cytochromes P450 of the CYP76F sub-family were recently shown to hydroxylate santalenes and bergamotene; however, these enzymes produced mostly (E)-santalols and (E)-α-exo-bergamotol. We hypothesized that different santalene/bergamotene hydroxylases evolved in S. album to stereo-selectively produce (E)- or (Z)-sesquiterpenols, and that genes encoding (Z)-specific P450s contribute to sandalwood oil formation if co-expressed in the heartwood with upstream genes of sesquiterpene biosynthesis. This hypothesis was validated by the discovery of a heartwood-specific transcriptome signature for sesquiterpenoid biosynthesis, including highly expressed SaCYP736A167 transcripts. We characterized SaCYP736A167 as a multi-substrate P450, which stereo-selectively produces (Z)-α-santalol, (Z)-β-santalol, (Z)-epi-β-santalol and (Z)-α-exo-bergamotol, matching authentic sandalwood oil. This work completes the discovery of the biosynthetic enzymes of key components of sandalwood fragrance, and highlights the evolutionary diversification of stereo-selective P450s in sesquiterpenoid biosynthesis. Bioengineering of microbial systems using SaCYP736A167, combined with santalene/bergamotene synthase, has potential for development of alternative industrial production systems for sandalwood oil fragrances.

Preliminary study: kinetics of oil extraction from sandalwood by microwave-assisted hydrodistillation

Sandalwood and its oil, is one of the oldest known perfume materials and has a long history (more than 4000 years) of use as mentioned in Sanskrit manuscripts. Sandalwood oil plays an important role as an export commodity in many countries and its widely used in the food, perfumery and pharmaceuticals industries. The aim of this study is to know and verify the kinetics and mechanism of microwave-assisted hydrodistillation of sandalwood based on a second-order model. In this study, microwave-assisted hydrodistillation is used to extract essential oils from sandalwood. The extraction was carried out in ten extraction cycles of 15 min to 2.5 hours. The initial extraction rate, the extraction capacity and the second-order extraction rate constant were calculated using the model. Kinetics of oil extraction from sandalwood by microwave-assisted hydrodistillation proved that the extraction process was based on the second-order extraction model as the experimentally done in three different steps. The initial extraction rate, h, was 0.0232 g L-1 min-1, the extraction capacity, CS, was 0.6015 g L-1, the second-order extraction rate constant, k, was 0.0642 L g-1 min-1 and coefficient of determination, R2, was 0.9597.