1. INTRODUCTION
Ayurveda uses medicinal plants to promote human welfare and treat a number of disorders, making it a healthy way of life. In India, ayurvedic medications are a traditional system of medicine that has a long history and is recognized by the government [1]. The system describes the medicinal plant, plant part, preparation technique, and application for the avoidance or mitigation of specific diseases, either alone or in combination with other plants. [2]. The World Health Organization (WHO) reports that over 80% of people in underdeveloped nations rely on these plants, particularly plant-based treatments, for their basic medical needs and employ traditional medicines and medicinal plants as therapeutic agents to preserve good health [3].
The plant Pterocarpus santalinus L., often called Red Sanders, Red Sandalwood, or Rakthachandan, is a member of the Fabaceae family. Red Sanders, is an endangered, essential medicinal angiosperm tree, is unique to the Eastern Ghats region of Andhra Pradesh, as well as the neighboring states of Karnataka and Tamil Nadu, hence endemic to India. It grows on arid, mountainous, frequently rocky soils in the Deccan Peninsula of India. The tree is renowned for its distinctive wood, which is exquisitely beautiful and colorful. The red pigment “santalin” and the yellow flavonoid “santal” found in the heartwood of the tree give it its distinctive red color. These compounds are used as coloring agents in pharmaceutical materials as well as evaluated for their therapeutic efficacies and used in drug formulations for the treatment of diseases like diabetes, skin conditions, inflammations, headaches, diaphoresis, dysentery diseases of the blood, stomach ulcers, and anthelmintics [5,39]. Among these species, only four are found in India, P. santalinus, Pterocarpus dalbergioides, P. marsupium, and P. indicus. The most endangered species is Pterocarpus santalinus [6]. Timber from P. santalinus is the species most valuable commercial component. It has historical and traditional importance and is used to make carvings, toys, and musical instruments [7].
1.1. Distribution
The Red Sanders is native to a specific area within the Eastern Ghats, primarily in the Rayalaseema region of Andhra Pradesh. This region hosts a distinct tract of forest where the species is endemic. Approximately 15.5 lakh harvestable Red Sanders trees are estimated to exist within these forests. Among them, about 1.6 lakh hectares (equivalent to 1,600 square kilometers) fall under Andhra Pradesh’s Protected Area Network. An additional estimated 9 lakh trees are found in reserve forest areas outside these protected zones. Beyond Andhra Pradesh, Red Sanders is also grown in small numbers in other Indian states, including Kerala, Maharashtra, Gujarat, Karnataka, Telangana, Tamil Nadu, Odisha, and West Bengal. P. santalinus is found in steep areas with a hot, arid climate. It thrives in the tropical regions of India, Taiwan, Philippines, Sri Lanka and China. In India, it is primarily found in the southern part of the Eastern Ghats, the Cuddapah, Kurnool, Prakasam, Nellore, and Chittor districts of Andhra Pradesh and restricted to Vellore and Chengalpattu districts of Tamil Nadu [Figure 1] [6,7].
 | Figure 1: Distribution of Red sanders in India. Highlighted region indicates the geographical restriction of the tree species in Eastern Ghats. [Click here to view] |
1.2. Botanical Description
P. santalinus is a small to medium-sized deciduous tree with extremely tough, dark purple heartwood that tastes bitter. The bark is dark brownish black and is divided into rectangular plates by strong vertical and horizontal characteristics. The heartwood is between one and two centimeters thick. Blaze is a pale yellow hue with several pink striations that give off copious amounts of thick, crimson, sticky gum. Dropping and hairless branchlets are seen. The leaves are typically egg-shaped or orbicular with 3 leaflets. The base is heart shaped or spherical. The apex might also have a sharp notch or be rounded. The margin is lustrous, hairless, and leathery. The flowers are yellow, bisexual, about 2 cm long, fragrant, and stalked in simple or sparingly branching racemes. Uneven orbicularity exits within pods, about 5×4.5 cm and are flat. The smooth, reddish-brown, kidney-shaped seeds measure between one and two centimeters in length [1].
P. santalinus is a small to medium-sized deciduous tree that has a dense, spherical crown that grows to a height of 10 to 15 m and a diameter of roughly 90 to 160 cm. When mature, the bark often has rectangular plates, is dark brown in hue, and is extensively fissured. It emits a crimson colored gum with multiple pink streaks when burned. The complex, pinnate leaves typically shed between January and March. As summer approaches, large yellow raceme flowers start to bloom and new foliage emerges. Temperature ranges from 11°C to 46°C, and rainfall ranges from 100 mm to 1,000 mm, which indicates a dry climate that prevails throughout the year. The slopes and soils in hilly areas, where the tree prefers to grow, are typically shallow, poor, stony, and well-drained [5].
1.3. Phytochemistry of P. santalinus
Alkaloids, flavonoids, terpenoids, phenolic chemicals, saponins, tannins, and glycosides were discovered in P. santalinus during phytochemical study. Additionally, non-specific metabolites such as triterpenes, sesquiterpenes, triterpene glucosides, isoflavones, and related phenolics were found. Specific phytoconstituents found in P. santalinus include beta sitosterol, lupeol, epicatechin, lignans, and pterostilbene’s [8, 9, 10]. In P. santalinus certain metabolites, such as beta-eudesmol, cryptomeridiol, isopterocarpalone, pterocarptriol, santalins A, B, and Y, and pterocarpalone, have tremendous medicinal potential [11]. Some of most important phytochemicals reported from Pterocarpus santalinus is represented in the Figure 2 and Tables 1, 2.
 | Figure 2: Chemical structure of some of the important phytochemicals isolated from the P. santalinus. [Click here to view] |
Table 1: Distribution of Pterocarpus species [2].
| Pterocarpus species | Distribution |
|---|---|
| Pterocarpus acapulcensis | Mexico, Columbia to Venezuela |
| Pterocarpus albopubescens | Zaïre |
| Pterocarpus amazonum | Bolivia, Brazil North, Brazil West-Central, Ecuador, Guyana, Peru, Venezuela |
| Pterocarpus angolensis | Zimbabwe,northern Botswana, Mozambique and Namibia and northwards into other parts of Africa. |
| Pterocarpus antunesii | Southern Angola, Namibia, Botswana,Malawi, Mozambique, Zambia and Zimbabwe |
| Pterocarpus bernaii. | Malawi, Mozambique, Zambia and Zimbabwe |
| Pterocarpus claessenii | Zaïre |
| Pterocarpus dalbergioides | Andaman group of Islands, India |
| Pterocarpus erinaceus | West and Central Africa Senegal in the west to the Central African Republic, Guinea, Togo and Benin |
| Pterocarpus gilletii | Zaïre |
| Pterocarpus indicus | SE Asia and the Pacific, from Southern Burma to the West to the Solomon Islands in the East, including Sumatra, West |
| Java, Borneo, Philippines, Sunda Islands, the Moluccas, New Guinea, and the Carolines | |
| Pterocarpus lucens | Senegal to Ethiopia and Uganda, and subsp. Antunesii (Taub.) Rojo, from southern Angola and northern Namibia to Mozambique. |
| Pterocarpus macrocarpus | Myanmar , Thailand, Laos and Cambodia to southern Vietnam |
| Pterocarpus marsupium | India, Sri Lanka, and parts of Nepal and Bhutan |
| Pterocarpus mildbraedii | Sierra Leone, Liberia, Côte d’Ivoire, Ghana, Benin, Nigeria,Cameroon, Equatorial Guinea, Gabon and the Usambara and Udzungwe Mountains (Tanzania) |
| Pterocarpus officinalis | Southern Mexico, Central America, the Caribbean, and northern South America |
| Pterocarpus orbiculatus | Central & Southern. Mexico |
| Pterocarpus rohri | Southern Mexico to Southern Tropical America |
| Pterocarpus rotundifolius | mesic and well-watered woodlands of Africa |
| Pterocarpus santalinoides | Senegal east to the Central African Republic and DR Congo, and in South America. |
| Pterocarpus santalinus | India (Southern portion of Eastern ghats, Andhra Pradesh and Tamil Nadu), Sri Lanka |
| Pterocarpus soyauxii | south-eastern Nigeria east to eastern DR Congo and south to northern Angola |
| Pterocarpus termannii | Gulf of Guinea |
| Pterocarpus tinctorius | Congo to Tanzania and Southern Tropical Africa |
| Pterocarpus villosus | Brazil Northeast |
| Pterocarpus zehntneri | Brazil Northeast, Brazil Southeast |
| Pterocarpus zenkeri | Cameroon |
Table 2: Most potential phytochemicals reported from Pterocarpus santalinus.
| Name of the Compound | Plant part | Reference |
|---|---|---|
| Acetyloleanolic aldehyde, Acetyl oleanolic acid | Sapwood | [22] |
| Lupenone, β-amyrone, epilupeol, β-amyrin, lupeol, stigmasterol, β-sitosterol | Leaves | [8,21] |
| Erythrodiol | Sapwood | [22] |
| Lupenone | Heartwood | [22] |
| Lupenediol | Bark | [8] |
| 3-Ketooleanane | Bark | [23] |
| Isoliquiritigenin(2,4,40 -trihydroxychalcone) | Stem | [9,16] |
| Marsupsin, pterosupin, liquiritigenin | Heartwood | [9] |
| Neoflavones I and II | Stem | [20] |
| Hydroxy-20,40,50,7-tetramethoxyisoflavone | Heartwood | [9] |
| 6-Hydroxy-7-methoxy-2H-chromen-2-one | Heartwood | [28] |
| Yellow 3-arylcoumarin derivative of santalin A | Stem | [26,27] |
| 5-Hydroxy-7-O-(3-methyl)-but-2enylcoumarin | Heartwood | [29] |
| Isopterocarpolone, pterocarptriol, pterocarpdiolone | Heartwood | [22] |
| Pterocarpol | Heartwood | [22,24] |
| Eudesmol; α-, β-, and γ-isomer;β-santalol | Heartwood | [22,24] |
| Canusenol K, Canusenol L, Hamahasal A.12,15-Dihydroxy curcumene.(3β)-eudesmen-4(14)--ene-3Ent-4(15)-eudesmen-1α | Heartwood | [25] |
| Cryptomeridiol | Heartwood | [22] |
| Calocedrin | Heartwood | [18] |
| Savinin | Heartwood | [18] |
| Pterostilbene | Heartwood | [15,16,17] |
| 7-Hydroxy-6-methoxy-coumarin-7-O-β-Dapiofuranosyl-(1--6)- β-D-glucopyranoside | Heartwood | [29] |
| 40,5-Dihydroxy-7-O-methyl-isoflavone-30-O-β-D-glucoside | Heartwood | [10] |
| 40,5-Dihydroxy-7-O-methyl-isoflavone-30-O-β-D-(300-E-cinnamoyl)-glucoside | Heartwood | [30] |
| 7-Hydroxy-6-methoxy-coumarin-7-O-α-Larabinopyranosyl-(1--3)-β-Dgalactopyranosyl-(l--6)-β-Dgalactopyranoside | Heartwood | [14] |
| Santalin A | Stem | [35,36] |
| (-)-Fistenidol, santarubin A, santarubin B | Stem | [36,37] |
| Santalin, santal | Heartwood | [34,37] |
| Melanoxin-7, Pterolinuses A–J Melanoxoin-14, S-30-Hydroxy-4,40- dimethoxydalbergione-15, Hydroxybenzoic acid | Heartwood | [32,33] |
| Para-hydroxybenzoicacid, gentisic acid, αresorcylic acid, β-resorcylic acid, vanillic acid | Heartwood | [31] |
The active portion of P. santalinus bark’s phytochemical examination revealed the presence of flavonoids, glycosides, and phenols. Animal models used for biological testing of these bioactive substances revealed strong antidiabetic efficacy by lowering blood glucose and glycosylated hemoglobin levels, enhancing hyperlipidemia, and reestablishing insulin levels [12]. Steroids, flavonoids, carbohydrates, and mostly triterpenes, including lupenone, βamyrone, epilupeol, β-amyrin, lupeol, stigmasterol, and β-sitosterol, were found in P. santalinus leaves after phytochemical study. Triterpenes had antibacterial, analgesic, antioxidant, and anti-inflammatory properties.[13].
The heartwood of P. santalinus was examined phytochemically, and the results showed the presence of alkaloids, glycosides, phenolic compounds, flavonoids, terpenoids, carbohydrates, saponins, and tannins [14]. Pterocarpol, pterocarptriol, santalins A, B, and Y, isopterocarpalone, pterocarpodiolones, βeudesmol, and cryptomeridiol are among the other extremely specific metabolites found in P. santalinus [11]. It has been discovered that Pterocarpus species are abundant in terpenoids and isoflavonoids, along with associated phenolic compounds like epicatechin, lupeol, and β-sitosterol [14].
The secondary plant metabolites known as stilbenes are produced by phenylpropanoid pathways. E-stilbene (trans) and Z-stilbene (cis) are the two stereoisomer forms of stilbenes, which are phenolic chemicals. Pterostilbenemethyle, a particular resveratrol stilbene found in P. santalinus heartwood, has anti-inflammatory, antioxidant, antitumor, and anticancer properties [15,16,17].
Lignins and lignans are another group of plant metabolites. Certain lignins found in P. santalinus heartwood, such as salvin, calocedrin, and eudesmin, are important for the plant’s defense against disease and insects [18]. Isoflavones are a class of secondary plant metabolites that are mostly present in P. santalinus and other Fabaceae members. Some of the isoflavones identified in P. santalinus include hydroxy-20,40,50,7-tetramethoxy- isoflavone, isoliquiritigenin (2,4,40-trihydroxychalcone) Marsupsin,pterosupin, liquiritigenin [16,19]. Neoflavones I and II were also present in the stem of P. santalinus [20].
Triterpenes, which are made up of three terpene molecules, are one of the most abundant and varied groups of plant metabolites. Important triterpenes that are identified in P. santalinus include lupenediol in leaves, lupenone, β-amyrone, epilupeol, β-amyrin, lupeol, stigmasterol, and betasitosterol in bark [8,21]. Erythrodiol in sapwood, acetyloleanolic aldehyde, and acetyloleanolic acid in heartwood [22]. 3-Ketoolenanewas is present in the bark of P. santalinus [23].Three isoprene units make up the class of terpenes known as sesquiterpenes. Sesquiterpenes are semiochemicals (that play a role in defense as pheromones or defense agents) in plants. Eudesmol; α-, β- and γ-isomer, β-santalol, pterocarpol, isopterocarpolone, pterocarptriol, pterocarpdiolone, and cryptomeridiol were some sesquiterpenes [22,24]. Canusenol K, canusenol L, hamahasal A, 12,15-dihydroxy curcumene, ent-4(15)-eudesmen-1α, and (3β)-eudesm-4(14)ene-3, are some of the sesquiterpenes discovered in P. santalinus [25].
One of the secondary metabolites in higher plants that is essential to pathogen defense and the response to abiotic stress is coumarins are one. The coumarin found in P. santalinus includes 3aryl coumarin in stem [26,27]. 6-hydroxy-7-methoxy-2H-chromen-2-one, and 5-hydroxy-7-O(3-methyl)-but-2-enylcoumarin in heartwood [28,29].
Thirty naturally occurring phenolic acids, mostly hydroxyl and polyhydroxy benzoic acids, have been shown to exhibit biological activity; of these, vanillic acid, gentisic acid, α- and β-resorcylic acid, and 3-hydroxybenzoic acid are of great importance to the pharmaceutical industry [29, 30, 31]. The heartwood of P.santalinus was found to include Pterolinuses A-J, melanoxin-7, melanoxoin-14, S-30-hydroxy-4, and 40-dimethoxydalbergione15, according to a comparison of nuclear magnetic resonance and mass spectrometry data. These neoflavonoids and benzofurans have anti-inflammatory and cytotoxic properties [33]. Some miscellaneous compounds, such as santalin and santalare, are present in the heartwood of P. santalinus [34]. Fistenidol, santarubin A, Santarubin B, and Santalin B are present in stem and Santalin Y can be found in the whole plant of P.santalinus [35, 36,37].
1.4. Pharmacological Potential of P. Santalinus
The pharmacology, ethnomedicinal, and phytochemical uses of P. santalinus were examined in earlier reviews. Due to the vast spectrum of biological activity of the bioactive chemicals found in the plant’s heartwood, P. santalinus may one day be used to treat a variety of ailments. The heartwood and bark exhibited hepatoprotective, anti-inflammatory, antibacterial, and anti-diabetic effects, according to studies done both in vitro and in vivo. The heartwood of the plant is highlighted in Ayurveda, an Indian system of traditional medicine, as being applied externally to cure diabetes, jaundice, inflammation, skin conditions, headaches, and wound healing. The key phytocompounds found in the heartwood and other plant extracts are reviewed in this paper, which also provides a summary of the most recent research on their chemical profiles and pharmacological effects [38].
1.5. Antimicrobial Activity
Numerous adverse effects are linked to chemically synthesized medications used for the treatment of microbial disease. Both human and phytopathogens infections have acquired ‘drug resistance’ against common medications. As a result, it is urgently necessary to develop new antibiotics that are both safe and potentially effective against resistant microorganisms. Many researchers have looked at the antibacterial properties of P. santalinus leaf and stem bark extracts. In comparison to leaf extracts, the stem bark extract exhibited the highest level of activity on a few types of test organisms. The extracts demonstrated activity that depended on concentration. The plant’s terpenoids, flavonoids, and steroids all had impressive MICs against Bacillus subtilis. This plant’s methanol extracts have been shown to be effective antibacterial agents. Plant extracts derived from ethanol had the largest zone of inhibition against Bacillus subtilis and excellent inhibition against Aspergillus niger.
1.6. Anti-Inflammatory Activity
It has been demonstrated that rats with induced hind paw edema react favorably to P. santalinus heart wood (3% formalin extracts). From the plant extracts, five novel benzofurans and pterolinuses were isolated. These demonstrated strong anti-inflammatory action. When given to carrageenan-induced rat paws, P. santalinus’s methanolic wood extract showed anti-inflammatory properties. The extracts of glycosides, essential oils, flavonoids, and polyphenolic components all provided anti-inflammatory action. Numerous studies using animal models have proved the plant’s intrinsic anti-inflammatory effects.
1.7. Anti-Oxidant Activity
P. santalinus ethanolic extract has shown strong antiulcer properties. This explains its ability to neutralize acids as well as its anti-inflammatory and antioxidant properties. Terpenoids, steroids, flavonoids, and carbohydrates are present in the methanolic extract of this plant. It significantly inhibited the DPPH radical (83.4% at a dosage of 25 mg/mL). Methanol extract exhibited impressive concentration-dependent free radical scavenging efficacy.
1.8. Anti-Diabetic Activity
Plant P. santalinus bark extract has caused a significant hypoglycemic response in experimental animals. The ethanolic fractions (dosage of 0.25 g/kg body weight) showed remarkable anti-diabetic activity on artificially created normal and diabetic rats. Furthermore, blood glucose levels in normal rats given the same amount did not alter, and the animals’ activity level was higher than that of diabetic rats given glibenclamide. Flavonoids, glycosides, and phenols showed considerable anti-hyperglycemic effect in experimental streptozotocin-induced diabetic rats by reducing blood glucose levels, lowering hyperlipidemia, and therefore restoring insulin levels. This was accomplished by decreasing gluconeogenesis and increasing glycolysis [4].
1.9. Other Pharmacological Activities
The plant is well-known for its distinctive wood, which has a stunning color, a delicate appearance, and exceptional technical features. The natural dye santalin, which is produced by the red wood, is used to color foodstuffs and pharmaceutical formulations. The decoction made from the heartwood is given numerous therapeutic characteristics in the ancient system of medicine. It has been used to induce vomiting as well as treat ulcers, mental disorders, and eye illnesses. It is known that the heartwood of Red sander trees has diaphoretic, aphrodisiac, antipyretic, anti-inflammatory, anthelmintic, tonic, hemorrhage, and dysentery-preventing properties. It’s been employed as a cooling agent as well. It has been claimed that an ethanol extract of stem bark has anti-hyperglycemic properties. For scorpion stings and snake bites, the wood is also used in combination with other medications [3].
Among the plants used to cure diabetes is P. santalinus. Diabetes has long been treated with drinking water from cups filled with P. santalinus wood. P. santalinus is helpful in treating bilious affections, skin conditions such as anthelmintic, aphrodisiac, and alexiteric, as well as conditions of the eyes, stomach, ulcers, blood, and vomiting. It also helps with diabetes mellitus and its symptoms. For persistent diarrhea, an infusion of the fruit’s decoction is used as an astringent tonic. The wood’s paste has been used as an external cooling agent to cure headaches, ulcers, inflammations, and mental abnormalities. Stem bark powder with soft porridge has been used to treat diarrhea. It is well known that the lignan extracted from the heartwood prevents the synthesis of tumor necrosis factor alpha and T-cell growth. Heartwood’s aurone glycosides have been identified as having anti-plasmodial activity and have being explored as a possible leishmanial medication. In CCl4-induced hepatotoxicity, methanol and heartwood aqueous extracts have demonstrated anti-hepatotoxicity. It has been claimed that P. santalinus, one of the constituents in Himoliv, a polyherbal and ayurvedic preparation, has hepatoprotective properties. Maximum action against Enterobacter aerogenes, Alcaligenes faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus was demonstrated by the stem bark extract. It is well known that ethanolic stem bark extract has anti-hyperglycemic properties. Additionally, the leaf extract shown greatest efficacy against P. aeruginosa, A. faecalis, E. aerogenes, and E. coli.