Ethnobotany, Phytochemistry, Biological Activities, and Health-Promoting Effects of the Genus Bulbophyllum

The genus Bulbophyllum is of scientific interest due to the phytochemical components and diverse biological activities found across species of the genus. Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests. In many cultures, the genus Bulbophyllum has a religious, protective, ornamenting, cosmetic, and medicinal role. Detailed investigations into the molecular pharmacological mechanisms and numerous biological effects of Bulbophyllum spp. remain ambiguous. The review focuses on an in-depth discussion of studies containing data on phytochemistry and preclinical pharmacology. Thus, the purpose of this review was to summarize the therapeutic potential of Bulbophyllum spp. biocompounds. Data were collected from several scientific databases such as PubMed and ScienceDirect, other professional websites, and traditional medicine books to obtain the necessary information. Evidence from pharmacological studies has shown that various phytoconstituents in some Bulbophyllum species have different biological health-promoting activities such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, and neuroprotective. No toxicological effects have been reported to date. Future clinical trials are needed for the clinical confirmation of biological activities proven in preclinical studies. Although orchid species are cultivated for ornamental purposes and have a wide traditional use, the novelty of this review is a summary of biological actions from preclinical studies, thus supporting ethnopharmacological data.


Introduction
Orchids are the largest group of angiosperms consisting of nearly 28,000 species with over 736 genera [1]. Although orchids are found in natural habitats in several parts of the world, their presence is decreasing due to great demand by the population [2]. Due to habitat destruction and indiscriminate collection, Orchid species are at a steady loss [3]. One of the most represented genera is Bulbophyllum ouars (Orchidaceae: subfamily Epidendroideae, subtribe Bulbophyllinae) with ca. 2,200 species distributed in Africa and Asia (China, Nepal, India, ailand, Laos, and Vietnam) [4]. e taxonomic history of Bulbophyllum has been complex since its establishment [5]. e great dimension and indefinite infrageneric systematics of this genus bring significant difficulties, reducing evolution, ecology, and morphology research [6]. Taxonomists have reported at least 24 closely related genera, classified based on floral morphology [7]. Only recently, molecular biology techniques have allowed recognizing this genus as monophyletic, i.e., belonging to a common ancestor [8].
Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests [9,10]. ey exclusively obtain water and nutrients from air, rain, and debris and thus must be able to overcome difficult environmental conditions by storing water in the pseudobulbs [11]. In addition to the economic importance attributable to ornamental uses, herbal medicinal properties of phytochemical substances of biological interest (such as flavonoids, sterols-terpenoids, and phenolic acids) in Bulbophyllum species have also been reported [12,13]. Several studies report both the phytochemical compounds and the molecules' biological effects extracted from Bulbophyllum leaf, pseudobulb, and root, for traditional medicine treatments [14].
In a continuous effort by researchers to discover the biological activities of Bulbophyllum species, we describe and summarize recent research in ethnobotanical knowledge, phytochemistry, and pharmacological properties, along with the limitations of the research in our article.

Methodology
To conduct this review, data were collected from research in several scientific databases, such as PubMed and Science-Direct, using the following MeSH terms: "Orchidaceae/ chemistry * ," "Plant Extracts/chemistry," "Drugs, Herbal/ chemistry," "Molecular Structure," "Anti-Inflammatory Agents/chemistry," "Antineoplastic Agents/chemistry." e study included documents written in English language that discussed ethnopharmacology, phytochemistry, and biological activities of these species. e taxonomy of the species has been validated according to the Plant List [15,16].

Botanical Aspects.
Plants of the genus Bulbophyllum are epilithic herbs, sympodial with roots creeping over the surface of the substrate or aerial, and filamentous to fibrous [17]. Orchid plants, such as Australian Bulbophyllum minutissimum, differ in size and weight from a gram to a few millimetres (1-1.5 mm across) [18]. e stems differentiate into rhizome and pseudobulb, and the leaves may be ovate, lanceolate, or orbiculate and variable in size on an individual plant [19]. Leaves are terminal on the pseudobulb (one or several per shoots) and conduplicate to the substrate. Recently, Piazza et al. [20] studied the vegetative anatomy of 13 species of Bulbophyllum belonging to sections Didactyle and Xiphizusa to elucidate the anatomical characters between and among the sections. e results revealed the anatomical differences among the species of both lipophilic secretion sections in young leaf trichomes and the presence of xeromorphic characters. Adaptations of both species to different environmental conditions were among the main differences described by the authors [20]. e inflorescence is racemose and presents many lateral flowers emerging from the rhizome, often at the base of the pseudobulb [19]. Some orchid species in the genus Bulbophyllum show an elaborated floral architecture, in addition to their characteristic floral odours that attract and bring specific pollinators [21]. e dorsal sepal is free, similar, or smaller than the lateral sepals. e latter are united basally to each other and a column foot forms a mentum, free or fused further [19]. e lateral petals are free and smaller than the dorsal sepals, and the lip of the flowers is trilobed with a large callus. In some species, the lip flaps with the wind, to simulate a fly shaking its wings to attract insects [9]. e labellum is hinged to the tip of the column foot; the lamina is either not lobed, obscurely 3-lobed, unornamented, or with 2 longitudinal keels. e column lacks the free filament and style; the column wings are fused to the column and reduced to teeth that project beside the anther [9]. e ovary, composed of three fused carpels and the mature seed pod, opens down the middle between the lines of juncture. e ovules are arranged along the ridges inside the ovary and do not develop until sometime after the flower [9]. Orchid flowers attract specific insect species by deceiving males with an imitation signal of female odour and mimetic appearance [22]. For example, the ginger orchid (Bulbophyllum patens King) flower releases a ginger essence called zingerone that attracts fruit flies sensitive to methyl eugenol and raspberry ketone [22,23]. Also, the flowers of Bulbophyllum apertum Schltr. release the volatile compound raspberry ketone with the function of attracting raspberry ketone-sensitive Bactrocera species [23]. e seeds of Bulbophyllum species consist of a dry, outer coat enclosing a small mass of undifferentiated cells that form a proembryo [17]. ey are fusiform, spindle, and narrowly ellipsoidal shaped and less than 1 mm in length without endosperm [24]. is extremely small and light unit can easily be carried in through air currents and may travel long distances before coming to rest [17]. Seed volume is related to seed size and Bulbophyllum species, and the higher seed volume is a result of greater width rather than testa length [24]. In natural conditions, the seeds have specific germination requirements provided by mycorrhizal fungi. For instance, seeds infected by a specific fungus can either germinate or be destroyed [25].
ere are different seed morphologies among the plants of the genus Bulbophyllum. For example, Bulbophyllum mysorense seeds are transparent, short, and spindle to oblong with blunt ends, and the testa cells have marginal clavate ridges, smooth on the outer face with longitudinally oriented cells resembling a twisted rope [26].

Bulbophyllum Species and Cultivation.
Every year, some new Bulbophyllum species are described, making this genus grow steadily [27]. Due to the extraordinary diversity, a general description would be too extensive [1,27]. Over 50 generic names have been proposed, in addition to Bulbophyllum [19].
In 2005, the Federal Ministry of Agriculture, Forestry, Environment, and Water Management as the CITES Management Authority of Austria elaborated three lists (names, accepted names, and the checklist) for the Bulbophyllum genus, produced by the Botanical Garden of Vienna [28]. e list is an approach to handle the vast number of species of this genus [28]. Recently, Bulbophyllum is into a single genus [7,19] Regarding the environmental conditions of cultivation, the warm temperature is suitable for Bulbophyllum plants that grow with a minimum of 22°C in winter, though species from temperate regions are grown 5-10 degrees cooler [30]. Light can be moderate to bright (2000 to 3500 candle feet): a higher light, which does not damage the leaves, seems to produce a better and more frequent flowering [30]. Bulbophyllum species tend to prefer a minimum of repotting using fern or cork slabs, baskets, and well-draining pots and the recommended impregnation media are sphagnum moss, coconut (flakes or coconut fibres), and tree fern both horizontally and vertically, whereas the relative humidity should be around 90% inside a greenhouse [31]. High relative humidity with a high air movement rate and constant fresh air are decisive parameters for the health and successful cultivation of the plants [31]. During the growth cycle, plants need adequate nutrition using standard fertilizers at 1/4 of the concentration given for houseplants [30]. e plants are usually rapid growers, reporting no major problems with pests. Propagation is through the division of the bulbs or via seeds of excellent germination rates [31]. Manual pollination of Bulbophyllum phalaenopsis, Bulbophyllum spies, and Bulbophyllum strontium has so far not been successful [31].

Geographical Distribution.
e taxa of the genus Bulbophyllum are pantropical, spreading across Africa, Australia, India, Madagascar, Southeast Asia, and tropical South and Central America [32] (Figure 1). e orchids, as epiphytes, are believed to be less adaptable to anthropogenic environmental variations than other plants [33]. e availability of the specificity host tree plays a central role in influencing the distribution and abundance of epiphytic orchids, often causing their unequal geographical distribution, even within a single tree [11].
Most of the Bulbophyllum species is epiphytes and is present in the virgin pantropical forest in the lower Montane forest at 1000 m above sea level [32]. However, a major number of species arise in the Indo-Malayan region [34]. Of 1000 species from India, 62 species are in the Northeastern region, 14 species in South India, and the remaining from other parts of India [35]. Madagascar is the hub of Bulbophyllum diversity (over 210 spp.), found mainly as epiphytes in a wide range of rainforest environments [36].
Madagascan Bulbophyllum molecular studies evidenced the existence of a monophyletic group of Late Miocene age with two major lineages: a species-rich core clade, mainly distributed in eastern rainforest of mid-to-high elevation (c. 800-1300 m), and a species-poor clade that is ecogeographically wide-ranging [37].
According to research, about 105 species of Bulbophyllum are present in China [38,39]. Bulbophyllum ouars is one of the largest genera among the orchid family, with around 2000 species in the tropical and subtropical zone of the world [40].  [40].
ese species are endemic of the Indochinese Peninsula, except for Bulbophyllum flavescens, which is widely distributed in western Malesia [40]. e "vinaceous orchid" (Bulbophyllum vinaceum Ames and C. Schweinf ) is a rare epiphytic plant endemic to the highlands of Borneo Island, such as the Crocker Range and Mt. Kinabalu of Sabah [21].

Ethnopharmacology
e usage of orchids in Ayurvedic or folklore treatment is common in many parts of the world, which raised immense attention to explore their pharmacological properties and bioactive constituents in-depth. e genus Bulbophyllum has an important role in many cultures acting as a religious, protective, ornamenting, cosmetic, and medicinal means. Leaves, pseudobulbs, and flowers of Bulbophyllum sp. have ethnobotanical importance and are used for various ailments, for both external and internal applications and administrations by tribal peoples. B. neilgherrense is an epiphytic plant used by the South Indian tribes to treat heart disease, leukoderma, skin allergy, and rheumatism; its pseudobulb is the most used part for traditional remedies. e uses of B. scaberulum in South African traditional medicine were observed for pain-related ailments, recommending further studies to explore the chemical profile and interactions between different classes of compounds and biological/pharmacological activities.
In Cameroon, Bulbophyllum falcatum and Bulbophyllum lupulinum are used against sorcery [2]. At the same time, leaves of Bulbophyllum falcatum are used for predictions, and the whole plant of Bulbophyllum simonii is used as a luck potion [2]. Bulbophyllum shanicum is offered in many religious ceremonies and used by Kayaladies for ornamenting their hair [42]. Bulbophyllum simonii and Bulbophyllum lilacinum are mixed in body lotion to keep the body fresh and cool [2,12].
Fluids from cleaned pseudobulbs of Bulbophyllum lilacinum are extracted by the press, kept in a sealed jar overnight, and then mixed with water and taken as a cool drink [12]. Powder of Bulbophyllum melinostachyum is recommended as anti-poisons [2].
In Zimbabwe, bark from species of the Bulbophyllum genus is tied around a fracture as a supporting pad [43]. Also, in different countries, many species of the Bulbophyllum genus are used as traditional herbal medicines (Table 1).
Both the quantitative and qualitative differences in chemical composition across species of the genus Bulbophyllum are due to the physiology and genetics of the species. However, other factors such as climate, soil, parts used, and phenological stages of the plants can also affect the secondary metabolite synthesis in these species.
Recent studies show that chemical composition can vary within the same species, in different environments, and in extraction systems.   Evidence-Based Complementary and Alternative Medicine carbohydrates. Ethanol and chloroform extracts show greater antifungal activity than petroleum ether and aqueous extracts, whereas the antibacterial activity in petroleum ether extract showed less effect than that reported in chloroform, ethanol, and aqueous extracts [61]. ere are many orchids with different medicinal properties and antibacterial activity. B. neilgherrense was tested for antibacterial activity against five bacterial species (Escherichia coli, Staphylococcus aureus, Bacillus pumilus, Pseudomonas aeruginosa, and Pseudomonas putida). Ethanolic, chloroform, and aqueous extracts (concentration of 5.50 w/v) from leaves and pseudobulbs were prepared for the disk diffusion method of antimicrobial sensitivity testing. e ethanolic extract of both leaves and pseudobulbs was more effective. e bacterial species P. aeruginosa and P. putida showed greater sensitivity to the pseudobulb ethanolic extract, while the ethanolic extract from leaves was effective against E. coli, S. aureus, and P. aeruginosa. However, all extracts were less effective than standard antibiotic streptomycin, when tested with the disk diffusion method in vitro [78].
B. affine has moderate bactericidal activity against Staphylococcus aureus (a common cause of skin infections) but none against Bacillus subtilis, Klebsiella pneumonia, Escherichia coli, or Vibrio cholera [79]. e orchid species B. careyanum and B. leopardinum are commonly used in burn treatments [80] although antimicrobial testing has not been reported for these species. In a similar study, B. neilgherrense exhibited moderate antibacterial activity against five infectious bacterial species [78], while promising antifungal activity against ten pathogenic fungal strains was reported from the same orchid species [81].
In the light of these results, the antibacterial activity of orchids is a good alternative for preventing/treating infections instead of using antibiotics, which have many side effects.

Antioxidant
Activity. Natural plant products have been used as poultices and/or anti-inflammatory drugs and antioxidants for many years [82,83].
Chinsamy et al. [84] reported antioxidant activity of Bulbophyllum scaberulum higher than other South African orchid species. e overall average antioxidant activity (% ANT) of B. scaberulum pseudobulb and root extracts was higher than 90%, which might validate the use of species to treat certain inflammatory disorders. e antioxidant effects and inhibition of acetylcholinesterase (AchE) enzyme from several indigenous orchid species (including B. Scaberulum) were evaluated. In their studies, the methanolic extracts of leaves, pseudobulbs, and roots of B. Scaberulum (similar to other orchids the extracts) showed high antioxidant potential with 100% average antioxidant activity (ANT) as compared to the standard BHT drug (95.88%), when tested with β-carotene bleaching assay. ey also found that the ethanol root extract at 5 and 0.5 mg/m exhibited significant mutagenic effects comparable to the 4NQO drug. Similarly, the dichloromethane extract of roots significantly inhibit AchE with the lowest IC 50 value of 0.02 mg/ml, while the ethanol extract showed less activity against AchE.
Recently, Sun et al. [85] purified several compounds from B. retusiusculum whole plants. New phenanthrene, bobulretin, and two bibenzyls were evaluated against α-glucosidase activity in vitro. All three compounds showed less than 20% inhibition when tested at the final concentration of 4.37 × 10 −4 mol/L.
Similarly, Bulbophyllum sp. exhibited higher antioxidant activity when compared to four other epiphytic orchids [86]. Plants of B. kaitense also presented good antioxidant activity and are considered a source of plant-derived antioxidants [87].
Polyphenols such as chrysin and pinobanksin found in orchid species of the genus Bulbophyllum have antioxidant effects [65,88,89], thus supporting their use in various heart diseases by the folklore traditions.
6.3. Anti-Inflammatory Activity. Nair et al. [54] used the pseudobulb powder of B. neilgherrense to examine analgesic and anti-inflammatory activities using different rat models. e pseudobulb powder mixed with honey and water revealed central analgesic activity against radiant heat-induced pain, moderate anti-inflammatory activity against carrageenan-induced acute inflammation, and mild or negligible activity against formalin-induced subacute inflammation and pain in rats. Pseudobulb contains flavonoids (chrysin and quercetin), glycosides, tannin, phenolic compounds, and calcium and may play a fundamental role in observed analgesic and anti-inflammatory activities [54].

Evidence-Based Complementary and Alternative Medicine
B. kaitense was examined in vitro for its anti-inflammatory activity using the human red blood cell (HRBC) method [77]. While petroleum ether, chloroform, and aqueous extracts exhibited various anti-inflammatory activities, the ethanolic extract of B. kaitense pseudobulbs showed potent anti-inflammatory activity. As south Indian orchids, some South African medicinal orchids also demonstrated notable anti-inflammatory effects, suggesting their potential in treating inflammation and related disorders.
A study conducted by Chinsamy et al. [84] reported that the dichloromethane, ethanol, and aqueous root extract of B. scaberulum had selective and significant COX-2 inhibition effects. Inhibition was 100.00, 93.31, and 58.09%, respectively, and dichloromethane and ethanol extract IC 50 values against COX-2 were 1.43 and 0.44 mg/ml, respectively. Surprisingly, the dichloromethane root extracts showed a greater inhibition performance than the commercial drug galantamine for COX-2. In contrast, water extracts from leaves and pseudobulbs exhibited moderate effects on COX-2, but no effect on COX-1.
e COX-2 inhibition effects of B. scaberulum suggested that it was due to condensed tannins present in the stems and/or roots [84].
Gowlis of Karnataka use a paste of pseudobulbs of Bulbophyllum neilgherrense Wight. for arthritis [90]. A study validated this trait and concluded that the pseudobulb powder had central analgesic activity against radiant heatinduced pain and moderate anti-inflammatory activity against carrageenan-induced acute inflammation [54]. e authors suggest that the potential mode of action of B. neilgherrense Wight. pseudobulb was due to the presence of flavonoids (chrysin and quercetin) in the plants [65] as several flavonoids such as hesperidin, luteolin, and quercetin have anti-inflammatory and analgesic effects [91]. Similarly, chrysin and quercetin have significant analgesic and antiinflammatory activities [92]. However, a 50% ethanolic extract of B. gymnopus Hook f. failed to show antimicrobial or anti-inflammatory activity and did not affect either respiration, cardiovascular system, or central nervous system, in experimental animals [93].
Aqueous pseudobulb extracts of B. scaberulum showed poor or no COX-1 and COX-2 inhibition [84]. Interestingly, the organic extracts (petroleum ether, dichloromethane, and ethanol) of B. scaberulum showed higher activity in the same study.
Bulbophyllum kaitense has been used in indigenous medicine by local healers of the Kolli hills. Its anti-inflammatory validation has been reported using human red blood cell (HRBC) membrane stabilization method [46]. e HRBC membrane stabilization assay uses the HRBC method as analogous to lysosomal membrane components, and thus, the inhibition of hypotonicity or heat-induced red blood cell membrane lysis may be taken as a measure of the anti-inflammatory activity mechanism of extracts.

Anticancer Activity.
Numerous studies report that Bulbophyllum species have in vitro cytotoxicity activity. e phenanthrenes isolated from Bulbophyllum odoratissimum and Bulbophyllum inconspicuum showed significant cytotoxicity against various cancer lines such as the human leukaemia cell lines K562, HL-60, and SMMC-7721 [59,94]. Similarly, dihydrodibenzoxepins isolated from Bulbophyllum kwangtungense also exhibited antitumour activities against HeLa and K562 human tumour cell lines [73]. Chen et al. [56] isolated and studied various phenolic compounds from Bulbophyllum odoratissimum as their inhibitory ability against the growth of human leukaemia cell lines K562 and HL-60, human lung adenocarcinoma A549, human hepatoma BEL-7402, and human stomach cancer SGC-7901. e results indicated a high activity against selective cell lines, i.e., in three compounds where densiflorol was the most active compound, followed by syringaldehyde and tristin [57]. e other compounds evaluated were weak or either inactive.
Biswas et al. [95] reported that Bulbophyllum sterile petroleum ether fraction induces apoptosis in vitro and ameliorates tumour progression in vivo, suggesting that the active fractions of bulbs and roots have anticancer activity likely by inducing apoptosis through the phospho-p53-dependent pathway [95]. e extract of B. kwantungense also exhibited antitumour activity in vitro against cultivated human cervical carcinoma cells (HeLa) [96]. Chen et al. [56] isolated phenanthrene derivative 3,7-dihydroxy-2,4,6-trimethoxyphenanthrene from B. odoratissimum, and its structure was elucidated by extensive chemical transformations and nuclear magnetic resonance (NMR) spectroscopy spectrum studies.
e isolated compound showed significant cytotoxicity against the growth of human leukaemia cell lines HL- 60 [1,3]dioxol-5-yl)ethyl)phenol (3MDP) and 6-(3-hydroxyphenethyl)benzo[d] [1,3]dioxol-4-ol (6HBD), previously purified from B. odoratissimum, were synthesized via the Wittig-Horner reaction and used for developing nine synthetic analogues by Zhang et al. [97]. 3MDP and 6HBD together with their two analogues bearing an amino acid moiety in place of the phenolic OH of 3MDP and 6HBD were found to have significant anti-proliferative activity selective to two cancer cell lines, SGC-7901 and KB, with IC 50 value of <10.0 μM, while the other analogues showed a markedly reduced cytotoxicity towards all tumour cell lines, SGC-7901, KB, and HT-1080.
Chen et al. [57] purified nine phenolic compounds, including moscatin, 7-hydroxy-2,3,4-trimethoxy-9,10dihydrophenanthrene, coelonin, densiflorol B, gigantol, batatasin III, tristin, vanillic acid, and syringaldehyde, from the ethyl acetate extract of B. odoratissimum whole plant and investigated the cell growth inhibition effects on different tumour cell lines such as human leukaemia cell lines K562 and HL-60, human lung adenocarcinoma A549, human hepatoma BEL-7402, and human stomach cancer SGC-7901. Except for three compounds such as densiflorol B, tristin, and syringaldehyde, all other compounds showed weak or no activity on tumour cells. Densiflorol B was the most active compound against all tumour cells showing the IC 50 values ranging from 0.08 to 3.52 μg/ml. Tristin displayed selective cytotoxicity against SGC-7901, with an IC 50 value of 2.08 μg/ ml, whereas syringaldehyde exerted a strong activity against BEL-7402 cells with an IC 50 value of 1.54 μg/ml.
Two new dimeric phenanthrenes, bulbophythrins A and B, were then purified from B. odoratissimum, and their inhibitory ability against the growth of the same tumour cell lines was evaluated, as previously tested by Chen and his coworkers [57], with both compounds exerting significant cytotoxicity against all tumour cell lines [59]. However, bulbophythrin A exhibited some selective cytotoxicity against HL-60 and BEL-7402 with IC 50 values of 1.27 × 10 −3 and 1.22 × 10 −3 μM, respectively, whereas bulbophythrin A appeared to be most active against A549 with an IC 50 value of 1.18 × 10 −3 μM, suggesting their potential use as a novel class of antitumour candidate in tumour disease.
Petroleum fraction, compared with the alcoholic extracts, from bulbs (PFB) and roots (PFR) of B. sterile, was found to be the most active in three different cancer cell lines, HCT-116, MDA-MB-231, and A549, by [95]. However, there was significant cytotoxicity in HCT-116 cells with IC 50 values of 94.2 and 75.7 μg/ml for PFB and PFR, respectively, likely attributed to the effects on the cell cycle G2/M phase with 32.6% and 49.4% arrest. In addition, PFB and PFR treatments showed 48% and 38% apoptosis, respectively, when tested with acridine orange/ethidium bromide (AO/EB) staining assay. eir apoptosis induction was carried out through phospho-p53-dependent pathway. Both fractions lowered tumour volume and increased life span and hepatic antioxidant level in Ehrlich ascites carcinoma (EAC) bearing mice, resulting in lower EACinduced mortality.
In a different report by Yang et al. [64], two compounds, a flavone C-glycoside and bibenzyl purified from B. retusiusculum tubers, did not show evident cytotoxicity on six cancer cell lines, including HL-60, SMMC-7721, A549, MCF-7, and SW-480. eir IC 50 value was greater than 40 μM, and their noncytotoxic effects were previously thought to be attributed to their structural differences to other bibenzyl compounds previously reported to have cytotoxic effects.

Neuroprotective Effect.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory impairment and cognitive deficit [98]. Various mechanisms, such as AChE inhibition, modification of monoamine levels, anti-amyloid aggregation, and antioxidant activities, are the strategies that have been employed for the amelioration of AD symptoms [99,100]. Of these, one of the major approaches has involved addressing the levels of acetylcholine in the AD-depressed brain using AChE inhibitors [101]. Most of the currently available drugs are AchEi, and some are related to natural products with an important therapeutic strategy for the treatment of AD. Many research groups have focused their studies on naturally occurring compounds from plants as potential sources of either new or more effective AChEi. Due to the presence of flavonoids and tannins, orchid extracts that display significant effects in anti-inflammatory, antioxidant, and AChE inhibitory assays could be potential natural plant products in the inflammatory treatment of neurodegenerative disorders.
Chinsamy et al. [84] reported anticholinesterase activity (EC 50 ) for different extraction solvents as 0.02 ± 0.00 and 0.26 ± 0.007 mg/ml, respectively, in dichloromethane and ethanol root extracts of B. scaberulum. e authors also found that B. scaberulum root extract effectively inhibited AChE as compared to the commercial product galantamine.
6.6. Other Activities. Myanmar women prepare a hair tonic and shampoo by mixing ground pseudobulbs of various species of Bulbophyllum with pulverized bark, seeds, and fruit (species not identified) when washing their hair. is mixture is claimed to cure dandruff, promote hair growth, and improve hair colour [102].
Imbricatin, a stilbenoid isolated previously from Bulbophyllum and other orchid genera, was one of three isolated stilbenoids recommended for use as skin photoprotectants based on their antioxidant, anti-inflammatory, and immunomodulatory effects [103].
A summarized scheme of the most representative biological activities is summarized in Figure 3.

Safety Data
No reports were found in the literature concerning health safety issues after the consumption of Bulbophyllum. is plant has been used in ethnomedicine and folk medicine by villagers in different conditions for ages; however, the toxicity profile of the Bulbophyllum species is still undiscovered. With the increasing cases of poisoning associated with the use of herbal medicines in many parts of the world in recent times [104], it is essential to ensure safety through toxicity assessment alongside active pharmacovigilance to promote their safe use and protect public health. erefore, it is necessary to identify the risks associated with the use of such herbal plants, and in this regard, the safety of these products has become an issue of great public health importance and thus a key moment for considering it in pharmacovigilance systems. erapeutic limitations of Bulbophyllum species are due to ignorance of long-term adverse effects, toxicity, and mutagenic potential. Future experimental pharmacological research is needed to further investigate the molecular mechanisms and action targets of the bioactive compounds contained in Bulbophyllum species. Another limitation is the lack of clinical trials.

Conclusion
In recent years, the genus Bulbophyllum is gaining the attention of plant researchers because of its rich phytochemical profile and variety of biological activities reported across species of the genus. Most Bulbophyllum species are epiphytic and found in habitats that range from subtropical dry forests to wet montane cloud forests. Plants belonging to the genus Bulbophyllum are mostly epilithic herbs and sympodial with roots creeping over the surface of the substrate or aerial, filamentous to fibrous. e genus Bulbophyllum has been utilized for protective, religious, cosmetic, ornamenting, and medicinal applications. Numerous investigations report the phytochemical compounds extracted from Bulbophyllum root, pseudobulb, and leaf, and their biological effect in traditional medicine treatments. Several phytochemical compounds of biological interest such as flavonoids, sterols-terpenoids, and phenolic acids have been reported in Bulbophyllum species. As summarized in the present review, the phytochemical composition of species of the genus Bulbophyllum offers insights into providing information on the antioxidant, anti-inflammatory, cytotoxic, antimicrobial, anticancer, and anticholinesterase activity. Furthermore, investigations are warranted to extract the various health-promoting phytochemicals and to identify their bioactivities, which will help to boost the utilization of Bulbophyllum species.
Data Availability e data supporting this review are from previously reported studies and datasets, which have been cited. e processed data are available from the corresponding author upon request. 12 Evidence-Based Complementary and Alternative Medicine