Chemical constituents and bioactivities of Blumea balsamifera (Sembung): a systematic review

Abstract

Blumea balsamifera (Sembung) is a very famous ethnic medicinal herbs and functional tea in many countries of Asia. Phytochemical investigations showed that B. balsamifera contains various type chemical components, including volatile oil, flavonoids, terpenoids, phenylpropanoids, polysaccharides, etc. B. balsamifera has many pharmacological activities such as antioxidation, antibiosis, antitumor, liver protection, anti-inflammation, analgesia, and wound healing. This paper reviewed the chemical constituents and pharmacological activities of B. balsamifera for the further research, development, and utilization of B. balsamifera.

Keywords:
Blumea balsamifera; phytochemical constituents; pharmacological activity

1 Introduction

Blumea balsamifera (L.) DC. is a very famous ethnic medicinal herbs and functional tea in many countries of Asia, such as China (named Ainaxiang), Malaysia (named Sembung), Philippines, Thailand, and Vietnam (Tan et al., 2020, 2023; Wang et al., 2023). The previous reports showed that B. balsamifera contains various type chemical components, including volatile oil, flavonoids, terpenoids, phenylpropanoids, polysaccharides, etc. and the chemical components of B. balsamifera have a variety of physiological activities, such as antioxidant, antibacterial, antifungal, anti-inflammatory, hypolipidemic, anti-infertility, liver protection, anti-diabetes, stomach protection, anti-tumor and so on (Tan et al., 2012; Widhiantara & Jawi, 2021).

The two main ingredients (L-Borneol and Blumea balsamiferae oleum) in Blumea balsamifera are the main components of many proprietary Chinese medicines such as Yinlishuang pills, Yankang tablets, Jinhoujian Spray, and Xinwei Zhitong Capsules. In addition, B. balsamifera is also widely used in the field of cosmetics based on its unique aromatic odor and burn treatment effect. This paper reviewed the chemical constituents and pharmacological activities of B. balsamifera for the further research, development, and utilization of B. balsamifera.

2 Chemical composition

There are more than 100 volatile or nonvolatile chemical components isolated from B. balsamifera (Chen et al., 2009; Pang et al., 2014a), including volatile oils, flavonoids, terpenoids, phenylpropanoids, steroids, etc., of which volatile oils, flavonoids, and sesquiterpenes are the most abundant and are the main chemical components of B. balsamifera, with a variety of in vitro and in vivo biological activities.

2.1 Essential oil

Essential oil is an important kind of chemical components with pharmacological activity in B. balsamifera. The main essential oil components include (-)-bromelain, trans-gastrolene, γ-eudesmol, α-eudesmol, anthocyanin, gastrolene oxide, and camphor (He et al., 2020; Yang et al., 2021). Although the categories of volatile components in B. balsamifera are similar due to the origin, harvesting time, and extraction method, there are some differences in the content of specific components (Yuan et al., 2016).

2.2 Flavonoids

Flavonoids are one of the more reported classes of components in B. balsamifera in recent years, and with a wide range of pharmacological activities have also greatly expanded the scope of clinical applications of B. balsamifera medicinal herbs(Pang et al., 2017). At present, scholars have isolated a total of 56 flavonoids from different parts of B. balsamifera, including dihydroflavonoids (compounds 1-8), dihydroflavonols (compounds 9-22), flavonoids (compounds 23-28), flavonols (compounds 29-50), chalcones (compounds 51, 52), paclitaxel (compounds 53, 54), and flavonoid dimers (compounds 55, 56). The names of these compounds are shown in Table 1, and their structures are shown in Figure 1.

Table 1
Flavonoids isolated from B. balsamifera (1-56).

No.	Compound name	Formula	Molecular weight	Part of plant	Type	Ref.
1	Eriodictyol	C15H12O6	288.26	Leaf	Dihydroflavonoids	(Zhao et al., 2007)
2	7-methyl-eriodictyol	C16H14O6	302.28	Leaf		(Osaki et al., 2005)
3	Blumeatin	C16H14O6	302.28	Aboveground part		(Chen et al., 2010b)
4	3',5,5',7-tetrahydroxyflavanone	C15H12O6	288.26	Aboveground part		(Chen et al., 2010b)
5	Liquiritigenin	C15H12O4	256.26	Leaf, Stem		(Huang et al., 2014)
6	Isohemiphloin	C21H22O10	434.39	Aboveground part		(Zhou et al., 2021)
7	2’,5,5’,7-tetrahydroxyflavanone	C15H12O6	288.26	Aboveground part		(Osaki et al., 2005)
8	3',4',5-trihydroxy-7-methoxyfavanone	C16H14O6	302.28	Aboveground part		(Chen et al., 2009)
9	Blumeatin A	C16H14O7	318.28	Leaf, Stem	Dihydroflavonols	(Zhao et al., 2007)
10	3,4',5-trihydroxy-3',7-dimethoxyflavanone	C17H16O7	332.31	Leaf		(Chen et al., 2009)
11	3,3',5-trihydroxy-4',7-dimethoxyflavanone	C17H16O7	332.31	Leaf		(Zhao et al., 2007)
12	3,3',4',5-tetrahydroxy-7-methoxyflavanone	C16H14O7	318.28	Leaf		(Chen et al., 2009)
13	3,3',5,5',7-pentahydroxyflavanone	C15H12O7	304.25	Leaf		(Gao et al., 2016)
14	2’,3,5,7-tetrahydroxy-5’-methoxyflavanone	C16H14O7	318.28	Aboveground part		(Osaki et al., 2005)
15	2’,3,5-trihydroxy-5’,7-dimethoxyflavanone	C17H16O7	332.31	Aboveground part		(Chen et al., 2009)
16	(2R, 3R)-dihydroquercetin-4′-methyl ether	C16H14O7	318.28	Leaf		(Chen et al., 2009)
17	Taxifolin	C15H12O7	304.25	Leaf, Branch		(Hu et al., 2018)
18	(2R,3R)-dihydroquercetin-4',7-dimethyl ether	C17H16O7	332.31	Leaf		(Chen et al., 2009)
19	(2R,3S)‐(−)‐4′‐O‐methyldihydroquercetin	C16H14O7	318.28	Aboveground part		(Nguyen & Nguyen, 2012)
20	5,4'-dihydroxy-3,7,3'-trimethoxydihydroflavone	C18H18O7	346.34	Leaf, Stem		(Huang et al., 2010)
21	5,7,3′,4′-tetrahydroxy-2-methoxy-3,4-flavandione 3-hydrate	C16H14O9	350.28	Leaf, Branch		(Hanh et al., 2021)
22	Catechin	C15H14O6	290.27	Leaf		(Chen et al., 2010a)
23	Luteolin	C15H10O6	286.24	Leaf	Flavonoids	(Zhao et al., 2007)
24	Diosmetin	C16H12O6	300.27	Leaf, Branch		(Yan et al., 2012)
25	Chrysoeriol	C16H12O6	300.27	Leaf, Branch		(Yan et al., 2012)
26	Luteolin-7-methyl ether	C16H12O6	300.27	Leaf		(Osaki et al., 2005)
27	Velutin	C17H14O6	314.29	Leaf		(Osaki et al., 2005)
28	4’,5-dihydroxy-7-methoxyflavone	C16H12O5	284.27	Leaf, Stem		(Huang et al., 2010)
29	Quercetin	C15H10O7	302.24	Aboveground part	Flavonols	(Chen et al., 2010b; Nguyen & Nguyen, 2012)
30	Ombuin	C17H14O7	330.29	Leaf		(Chen et al., 2009)
31	Tamarixetin	C16H12O7	316.27	Leaf		(Cao et al., 2007; Hu et al., 2018; Saewan et al., 2011)
32	Rhamnetin	C16H12O7	316.26	Leaf		(Chen et al., 2009)
33	3,5,7-trihydroxy-3',4'-dimethoxyflavone	C17H14O7	330.29	Leaf, Branch		(Tan et al., 2012)
34	3,5-dihydroxy-3',4',7-trimethoxyflavone	C18H16O7	344.32	Leaf, Branch		(Yan et al., 2012)
35	7,5′-Dimethoxy-3,5,2′-trihydroxyflavone	C17H14O7	330.29	Aboveground part
36	Chrysosplenol C	C18H16O8	350.32	Leaf, Branch		(Yan et al., 2012)
37	Hyperoside	C21H20O12	464.38	Leaf, Branch		(Tan et al., 2012)
38	Isoquercitrin	C21H20O12	464.38	Leaf, Branch		(Tan et al., 2012)
39	Ayanin	C18H16O7	344.32	Leaf		(Osaki et al., 2005)
40	Quercetin-3,7,3'-trimethyl ether	C18H16O7	344.32	Leaf		(Osaki et al., 2005)
41	Kumatakenin	C17H14O6	314.29	Leaf, Stem		(Huang et al., 2014)
42	Quercetin-3,7-dimethyl ether	C17H14O7	330.29	Leaf		(Osaki et al., 2005; Yuan et al., 2018)
43	Quercetin-3,3', 4'-trimethyl ether	C18H16O7	344.32	Aboveground part		(Chen et al., 2010a; Nguyen & Nguyen, 2012)
44	4',5,7-trihydroxy-3,3'-dimethoxyflavone	C17H14O7	330.29	Leaf		(Hu et al., 2018; Tan et al., 2012)
45	Quercetin-3,4'-dimethyl ether	C17H14O7	330.29	Leaf		(Osaki et al., 2005)
46	3',4',5,7-tetrahydroxy-3-methoxyflavone	C16H12O7	316.26	Leaf, Branch		(Tan et al., 2012)
47	3',4',5-trihydroxy-3,7 -dimethoxyflavone	C17H14O7	330.29	Leaf		(Bouktaib et al., 2002)
48	3,3',4',5-tetrahydroxy-7-methoxyflavone	C16H12O7	316.27	Leaf		(Cao et al., 2007)
49	Isorhamnetin-3-O-β-D-galactopyranoside	C22H22O12	478.41	Branch		(Zhang & Tan, 2007)
50	Rutin	C27H30O16	610.52	Leaf		(Zhu et al., 2003)
51	Davidigenin	C15H14O4	258.27	Aboveground part	Chalcones	(Chen et al., 2010b)
52	Davidioside	C21H24O9	420.41	Aboveground part		(Chen et al., 2010b)
53	Glycyrol	C21H18O6	366.36	Leaf, Stem	Paclitaxel	(Huang et al., 2014)
54	Isoglycyrol	C21H18O6	366.36	Leaf, Stem		(Huang et al., 2014)
55	3-O-7″-biluteolin	C30H18O12	570.46	Leaf	Flavonoid dimer	(Ali et al., 2005)
56	7,4′,4″-tri-O-methylamentoflavone	C33H24O10	580.53	Aboveground part		(Tan et al., 2013)

Figure 1
Flavonoids isolated from B. balsamifera.

In addition, in order to improve the production of flavonoid active ingredients in B. balsamifera in terms of biosynthesis, Xia et al. (2016) compared the transcriptome sequencing results of B. balsamifera with those of the biosynthetic pathways of flavonoids in other higher plants in the KEGG database and predicted that the metabolic pathway of flavonoids in B. balsamifera, and the key enzymes were CHS and chalcone isomerase, which provide a direction for further research on the biosynthesis of flavonoids in B. balsamifera.

2.3 Terpenoids

Terpenoids are a common class of compounds in B. balsamifera. Their cytoskeleton types include Monoterpenoids, sesquiterpenes, diterpenes, triterpenes and so on. Sesquiterpene lactone has attracted attention because of its cytotoxicity and potential antitumor activity. L-borneol, a famous traditional Chinese medicine, is a kind of bicyclic monoterpene, and its important plant source is B. balsamifera. At present, 5 sesquiterpenes, 51 sesquiterpenes and 5 diterpenes were isolated from B. balsamifera, and 2 ursolane triterpenes were isolated from the aboveground part of B. balsamifera. The name of the compound is shown in Table 2, and the chemical composition and structure are shown in Figure 2.

Table 2
Terpenoids isolated from B. balsamifera (57-118).

No.	Compound name	Formula	Molecular weight	Part of plant	Type	Ref.
57	2,6-dimethyl-octa-1,7-diene-3,6-diol	C10H18O2	170.25	Leaf	Monoterpenoids	(Xiong et al., 2022)
58	L-borneol	C10H18O	154.25	Leaf		(Wang et al., 2014)
59	Balsamiferoside B	C16H27NaO9S	418.43	Leaf, Branch		(Hanh et al., 2021)
60	(1S,2R,4S)-borneol-β-D-glucopyranoside	C16H28O6	316.39	Leaf, Branch		(Hanh et al., 2021)
61	(–)-angelicoidenol 2-O-β-D-glucopyranoside	C16H27O7	331.38	Leaf, Branch		(Hanh et al., 2021)
62	2,3-dimethyloxiranecarboxylic acid (1R,3R,5E,10S)-10-hydroxy- 6,10- dimethyl -3- (1-methylethyl)-4,9-dioxocyclodec-5-en-1-yl ester	C20H30O6	366.45	Leaf	Sesquiterpenes	(Osaki et al., 2005)
63	1,9-dihydroxy-4-eudesmen-6-one	C15H24O3	252.35	Leaf		(Chen et al., 2009)
64	1-ang-4,7-dihydroxyeudesmane	C20H34O4	338.49	Leaf		(Chen et al., 2009)
65	cryptomeridiol	C15H28O2	240.39	Leaf		(Ragasa et al., 2005)
66	Blumealactones A	C20H28O6	364.44	Leaf		(Chen et al., 2009)
67	Blumealactones B	C20H28O6	364.44	Leaf		(Chen et al., 2009)
68	Blumealactones C	C17H24O6	324.37	Leaf		(Chen et al., 2009)
69	2-methylbut-2-enoic acid(3aR,4S,5R,7R,8aS)-decahydro-3a,4-dihydroxy-4-methyl-7-(1-methylethyl)-1-methylidene-8-oxoazulen-5-yl ester	C20H30O5	350.46	Leaf		(Osaki et al., 2005)
70	Blumeaene A	C20H30O5	350.46	Aboveground part		(Chen et al., 2010b)
71	Blumeaene B	C20H30O5	350.46	Aboveground part		(Chen et al., 2010b)
72	Blumeaene C	C19H30O5	338.44	Aboveground part		(Chen et al., 2010b)
73	Blumeaene D	C21H32O5	364.48	Aboveground part		(Chen et al., 2010b)
74	Blumeaene E	C19H28O6	352.43	Aboveground part		(Chen et al., 2010b)
75	Blumeaene F	C20H30O6	366.45	Aboveground part		(Chen et al., 2010b)
76	Blumeaene G	C20H30O5	350.46	Aboveground part		(Chen et al., 2010b)
77	Blumeaene H	C19H30O5	338.44	Aboveground part		(Chen et al., 2010b)
78	Blumeaene I	C20H30O6	366.45	Aboveground part		(Chen et al., 2010b)
79	Blumeaene J	C20H32O7	384.47	Aboveground part		(Chen et al., 2010b)
80	Blumpene B	C20H32O5	352.47	Aboveground part		(Ma et al., 2018)
81	Blumpene C	C19H34NO5	356.24	Aboveground part		(Ma et al., 2018)
82	Blumpene D	C21H33O5	365.22	Aboveground part		(Ma et al., 2018)
83	Blumeaene E1	C20H30O6	366.45	Leaf		(Shirota et al., 2011)
84	Blumeaene E2	C20H30O6	366.45	Leaf		(Shirota et al., 2011)
85	Blumeaene K	C20H32O7	384.47	Leaf		(Shirota et al., 2011)
86	Blumeaene L	C17H26O5	310.39	Leaf		(Shirota et al., 2011)
87	Blumeaene M	C20H30O6	366.45	Leaf		(Shirota et al., 2011)
88	Balsamiferine E	C20H32O5	352.46	Aboveground part		(Xu et al., 2012)
89	Balsamiferine F	C21H32O5	364.48	Aboveground part		(Xu et al., 2012)
90	Balsamiferine G	C21H32O5	364.48	Aboveground part		(Xu et al., 2012)
91	Balsamiferine H	C15H24O4	268.35	Aboveground part		(Xu et al., 2012)
92	Balsamiferine I	C20H30O5	350.45	Aboveground part		(Xu et al., 2012)
93	Balsamiferine J	C20H30O5	350.45	Aboveground part		(Xu et al., 2012)
94	Balsamiferine N	C20H31ClO6	402.91	Leaf		(Xiong et al., 2022)
95	Balsamiferine O	C21H34O7	398.50	Leaf		(Xiong et al., 2022)
96	Blumeaene N	C20H30O6	366.45	Leaf		(Yong et al., 2019)
97	Balsamiferine K	C20H32O7	384.47	Leaf, Branch		(Hanh et al., 2021)
98	Inuchinenolide B	C17H22O5	306.36	Leaf, Stem		(Huang et al., 2014)
99	Neogaillardin	C17H22O6	322.36	Leaf, Stem		(Huang et al., 2014)
100	Cryptomeridiol	C15H28O2	240.39	Leaf		(Ragasa et al., 2005)
101	Balsamiferine D	C21H36O3	336.52	Aboveground part		(Ma et al., 2018)
102	Samboginone	C15H22O3	250.34	Leaf		(Shirota et al., 2011)
103	Balsamiferine B	C15H22O3	252.35	Aboveground part		(Xu et al., 2012)
104	Balsamiferine C	C15H22O3	250.34	Aboveground part		(Xu et al., 2012)
105	1β,4β,7α-trihydroxyeudesmane	C15H28O3	256.39	Leaf, Branch		(Hanh et al., 2021)
106	6,15α-epoxy-1β,4β-dihydroxyeudesmane	C15H26O3	254.37	Leaf, Branch		(Hanh et al., 2021)
107	β-caryophyllene-8R,9R-oxide	C15H26O	220.36	Leaf		(Saifudin et al., 2012)
108	(4R,5R)-4,5-dihydroxycaryophyll-8(13)-ene	C15H26O2	238.37	Aboveground part		(Ma et al., 2018)
109	Balsamiferine P	C20H28O5	348.44	Leaf		(Xiong et al., 2022)
110	Balsamiferine Q	C20H28O5	348.44	Leaf		(Xiong et al., 2022)
111	Balsamiferine R	C20H30O6	366.45	Leaf		(Xiong et al., 2022)
112	Balsamiferine A	C20H29ClO5	384.90	Aboveground part		(Xiong et al., 2022)
113	Blumpene A	C20H34O2	306.49	Aboveground part	Diterpenoids	(Ma et al., 2018)
114	Sterebin P1	C20H34O4	338.49	Aboveground part		(Ma et al., 2018)
115	Austroinulin	C20H34O3	322.49	Leaf		(Xiong et al., 2022)
116	(7S,12Z)-12,14-labdadiene-7,8-diol	C20H34O2	306.49	Aboveground part		(Ma et al., 2018)
117	Sterebin A	C19H32O3	308.46	Leaf		(Pang et al., 2019)
118	Ursolic acid	C30H48O3	456.71	Aboveground part	Triterpenes	(Zhou et al., 2021)
119	Ursolic acid lactone	C30H46O3	454.70	Aboveground part		(Zhou et al., 2021)

Figure 2
Terpenoids isolated from B. balsamifera.

2.4 Phenylpropanoids

Fourteen common phenylpropanoids and one coumarin were isolated from B. balsamifera, among which the simple phenylpropanoids existed as esters or glycosides. Phenylpropanoids in B. balsamifera are shown in Table 3 and Figure 3.

Table 3
Phenylpropanoids isolated from B. balsamifera (120-134).

No.	Compound name	Formula	Molecular weight	Part of plant	Ref.
120	3,5-O-dicaffeoylquinic acid ethyl ester	C27H28O12	545.10	Leaf	(Yuan et al., 2019)
121	3,5-O-dicaffeoylquinic acid methyl ester	C26H26O12	531.20	Leaf	(Yuan et al., 2019)
122	3,4-O-dicaffeoylquinic acid methyl ester	C26H26O12	531.20	Leaf	(Yuan et al., 2019)
123	3,4-O-dicaffeoylquinic acid	C25H24O12	515.11	Leaf	(Yuan et al., 2019)
124	3,5-O-dicaffeoylquinic acid	C25H24O12	515.11	Leaf	(Yuan et al., 2019)
125	1,3,5-tri-O-caffeoylquinic acid	C34H30O15	723.48	Leaf	(Yuan et al., 2019)
126	Ethyl caffeate	C11H12O4	208.21	Leaf	(Pang et al., 2019)
127	p-Hydroxycinnamic acid	C9H8O3	164.16	Leaf	(Pang et al., 2019)
128	Docosyl caffeate	C31H52O4	488.74	Leaf, Stem	(Huang et al., 2014)
129	Caffeic acid	C9H8O4	180.16	Leaf	(Yuan et al., 2018)
130	Methyl 3,4-dihydroxyphenyl lactate	C10H12O5	212.20	Aboveground part	(Zhou et al., 2021)
131	Balsamiferoside A	C16H21NaO10S	428.38	Leaf, Branch	(Hanh et al., 2021)
132	Eugenyl-O-β-D-glucoside	C16H22O7	326.35	Leaf	(Pang et al., 2019)
133	4-allyl-2,6-dimethoxyphenol glucoside	C17H24O8	356.37	Leaf	(Pang et al., 2019)
134	6,7-dihydroxycoumarin	C9H6O4	178.14	Leaf	(Pang et al., 2019)

Figure 3
Phenylpropanoids isolated from B. balsamifera.

2.5 Others

In addition to the above chemical components, it was found that B. balsamifera contains steroid compounds: β-sitosterol, stigmasterol, daucosterol, ergosterol peroxide, 4,22-stigmastadiene-3-one, 2-hydroxy-4,6-dimethoxyacetophenone, 2,4-dihydroxy-6-methoxyacetophenone, paraben, phytol, β-carotene, lutein, hentriacontane, et al (Table 4, Figure 4).

Table 4
Other compounds isolated from B. balsamifera (135-154).

No.	Compound name	Formula	Molecular weight	Part of plant	Ref.
135	β-Sitosterol	C29H50O	414.72	Leaf	(Chen et al., 2020; Zhao et al., 2007)
136	Stigmasterol	C29H48O	412.70	Leaf	(Zhao et al., 2007)
137	Daucosterol	C35H60O6	576.86	Aboveground part	(Tan et al., 2013)
138	Ergosterol endoperoxide	C28H44O3	428.66	Aboveground part	(Zhou et al., 2021)
139	4,22-Stigmastadiene-3-one	C29H46O	410.69	Leaf	(Zhang et al., 2015)
140	2-Hydroxy-4,6-dimethoxyacetophenone	C10H12O4	196.20	Aboveground part	(Zhou et al., 2021)
141	2,4-Dihydroxy-6-methoxyacetophenone	C9H10O4	182.18	Leaf, Branch	(Tan et al., 2012)
142	5,7-Dihydroxychromone	C9H6O4	178.14	Leaf, Branch	(Tan et al., 2012)
143	Paraben	C7H6O3	138.12	Aboveground part	(Tan et al., 2013)
144	2,5-dihydroxybenzoic acid	C7H6O4	154.12	Aboveground part	(Tan et al., 2013)
145	phytol	C20H40O	296.54	Aboveground part	(Tan et al., 2013)
146	icthyothereol acetate	C16H16O3	256.30	Leaf	(Ragasa et al., 2005)
147	β-Carotene	C40H56	356.89	Leaf	(Ragasa et al., 2005)
148	Lutein	C40H56O2	568.89	Leaf	(Ragasa et al., 2005)
149	Protocatechualdehyde	C7H6O3	138.12	Leaf	(Pang et al., 2019)
150	Protocatechuic acid	C7H6O4	154.12	Leaf	(Pang et al., 2019)
151	(4R)-4-(3-Oxo-1-buten-1-ylidene)-3α,5,5-trimethylcyclohexane-1α,3β-diol	C13H20O3	224.30	Leaf	(Pang et al., 2019)
152	4-(4-hydroxyphenoxy)phenol	C12H10O3	202.21	Leaf	(Saifudin et al., 2012)
153	3-(hydroxyecetyl)indole	C24H39NO	357.58	Leaf	(Pang et al., 2019)
154	Hentriacontane	C31H64	436.84	Leaf	(Zhang et al., 2015)

Figure 4
Other compounds isolated from B. balsamifera.

3 Pharmacological activities

The previous pharmacological activity investigations on the whole plant of B. balsamifera and its crude extracts or chemical components found various pharmacological activities such as antioxidant, antibacterial, antitumor, hepatoprotective, anti-inflammatory, analgesic and wound healing promotion. Different chemical components show different pharmacological effects, such as: flavonoids play a certain role in antioxidation, antitumor, protect acute liver injury, promote blood aggregation and resist radiation. L-borneol and camphor in the volatile oil have good antibacterial, vasodilating and skin penetration promoting effects.

3.1 Antioxidant

Flavonoids and polyphenols are the main components of the antioxidant in B. balsamifera (Fazilatun et al., 2005; Pang et al., 2014c). Nguyen et al. (2004) investigated the effect of three crude extracts (methanol, methanol-water (1:1), and water) in inhibiting xanthine oxidase and found that among the three crude extracts, methanol extract was the most effective, methanol-water was the second most effective, and water was the least active. Nessa et al. (2004) further investigated the antioxidant aspects of the crude extracts of B. balsamifera and concluded that different crude extracts of B. balsamifera have different degrees of antioxidant activity. Based on the above experimental results, Fazilatun Nessa inferred that the antioxidant activity of the flavonoids in B. balsamifera is mainly related to the number of hydroxyl groups, and the antioxidant activity of flavonoids containing one free hydroxyl group is greater than that of the methylated compounds (Fazilatun et al., 2005). In addition, Hu et al. (2018) found the strong antioxidant activity of flavonoids in B. balsamifera leaves by DPPH radical scavenging assay. Zhou et al. (2020) demonstrated that the antioxidant capacity was related to the presence of polyphenolic compounds by the effector surface method and Huihui & Jin (2013) found the strong antioxidant activity of essential oil of B. balsamifera leaves after DPPH radical scavenging assay, β-carotene bleaching assay and thiobarbituric acid assay. The above studies indicated that the essential oil of B. balsamifera has significant antioxidant activity and has the potential to be a natural antioxidant for food and cosmetics.

3.2 Antibacterial

Huihui & Jin (2013) confirmed that the essential oil had inhibitory activity against Staphylococcus aureus, Aspergillus flavus, Candida albicans, Enterobacter, Salmonella and Listeria monocytogenes. And related studies found that B. balsamifera extract and volatile oil have anti-bacterial and fungal effects: n-hexane extract has inhibitory effect on Enterobacter cloacae and Staphylococcus aureus, dichloromethane extract has an inhibitory effect on Enterobacter cloacae, while volatile oil has a strong inhibitory effect on Bacillus cereus, Staphylococcus aureus and Candida albicans (Sakee et al., 2011). Volatile oil can destroy the integrity of the Staphylococcus aureus cell membrane, change its cell membrane permeability, inhibit bacterial nucleic acid and protein synthesis, cause amino acid metabolism disorder, and affect the activity of various enzymes and substance transport (Yang et al., 2021). Wang et al. (2019) isolated 15 monomer compounds from ethyl acetate, mainly flavonoids, and evaluated their antibacterial activity. It was found that the antimicrobial activity of vanillin against Staphylococcus aureus was the strongest, and the minimum inhibitory concentration (MIC) was 32 μg / mL. In addition, He et al. (2020) studied the in vitro bacteriostatic effect of essential oil on Haemophilus parasuis and evaluated the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the essential oil. Wen et al. (2015) found that the extract of B. balsamifera residue has good antibacterial activity in vitro, and its chloroform extract has a significant inhibitory effect on Escherichia coli and type B Hemolytic streptococcus. The above studies show that B. balsamifera extract has a certain inhibitory effect on several infectious and toxin-producing microorganisms and can be used to prevent and treat microbial diseases.

3.3 Antitumor

Toshio et al (Norikura et al., 2008a, b) found that methanolic extract of B. balsamifera (BME) inhibited the growth of rat and human hepatocellular carcinoma cells. In addition, BME reduced the levels of proliferation-inducing ligands that stimulate tumor cell growth, suggesting a potential therapeutic effect of BME in patients with hepatocellular carcinoma. Hu et al. (2018) used cervical cancer (HeLa), breast cancer (MCF-7), lung cancer (A549), gastric cancer (MGC-803), and colon cancer (COLO-205) cell lines as donor cell lines and screened the cytotoxic activity of two sesquiterpene lactones isolated and purified from B. balsamifera using MTT method. The results showed that both Blumeaene E and Blumeaene N have cytotoxic activity.

3.4 Hepatoprotective effect

Xu & Zhao (1998) investigated the protective effects of 5,3',5'-trihydroxy-7-methoxydihydroflavone (BF-I) and four compounds (BF-II, BF-III, BF-IV, BF-V) obtained by structural modification of BF-I on acute liver injury. The results demonstrated that all five compounds had significant protective effects against acute liver injury caused by CCl4, AAP and TAA in rats, with BF-II showing the strongest activity, followed by BF-I, and then BF-III, BF-IV and BF-V. Zhao & Xu (1997) conducted a study on the pharmacological activity of BF-I and its structural modifiers and found that dihydroflavonoids have a strong inhibitory effect on lipid peroxidation. Pu et al. (2000) further demonstrated the protective effect of five dihydroflavonoids against CCl₄ or cysteine-induced lipid peroxidation in hepatocytes.

3.5 Anti-inflammatory and analgesic

In vivo experiments showed that essential oil of B. balsamifera significantly inhibited xylene-induced auricular swelling in mice, reduced the number of twists in acetic acid-induced mice, decreased the content of prostaglandin E2 in the inflammatory tissue of dimethylamine-induced mouse ears, and enhanced the activity of superoxide dismutase in mouse serum (Ma et al., 2016; Yi et al., 2016). In vitro experiments showed that essential oil significantly improved the morphological changes of LPS-induced RAW264.7 macrophages and reduced apoptosis. In addition, essential oil significantly inhibited the expression of leukocyte differentiation antigen 14, Toll-like receptor 4, myeloid differentiation primary response gene 88, and NOD-like receptor thermoprotein structural domain-associated protein 3 inflammatory vesicles in the NFκB signaling pathway (Liao et al., 2021). Through a comparative study of the anti-inflammatory effects of B. balsamifera herbs from different origins in Guizhou, Li et al. (2018) found that all the herbs from different origins also had certain anti-acute and chronic inflammatory effects. Cai et al. (2021) found that linalool and trans-stilbene are important anti-inflammatory components of essential oil, both of which can inhibit the release and expression of cellular inflammatory factors and inflammatory mediators.

3.6 Promotion of wound healing

By exploring the healing effect of essential oil on a rat deep second-degree burn model, Fan et al. (2015) found that essential oil treatment significantly reduced the water content of burned rat tissues, shortened the crusting time, accelerated healing, and significantly increased the expression of growth factors in tissues. Pang et al. (2014b) found that diluted essential oil promoted capillary regeneration, blood circulation, collagen deposition, granulation tissue formation, epithelial deposition and wound contraction by observing the effect of essential oil of B. balsamifera on wound healing in mice. The mechanism of action may be related to the induction of neuropeptide substance P secretion and mesenchymal cell proliferation and differentiation. However, undiluted essential oil may lead to skin thickening and sclerosis, inhibition of collagen synthesis and delayed skin wound healing. total flavonoids of B. balsamifera also promote skin wound healing in rats and the mechanism of action is related to increased expression levels of vascular endothelial growth factor, transforming growth factor β and hydroxyproline content at different stages of healing (Pang et al., 2017).

3.7 Hypoglycemia

Yan et al. (2014) found that the aqueous solutionof B. balsamifera (BBW) after extraction of volatile oil and ethyl acetate extract (BBE) of the alcoholic extract of the pomace after extraction of volatile oil had an inhibitory effect on α-glucosidase. Hu et al. (2018) obtained nine flavonoids from the leaves of B. balsamifera, 5 of which showed inhibitory effects on α-glucosidase. In addition, the aqueous and methanolic extracts of B. balsamifera also inhibited protein tyrosine phosphatase 1B with IC50 of 2.26 and 5.73 μg/mL, respectively (Saifudin et al., 2013, 2012).

3.8 Other pharmacological activities

Numerous studies have shown that B. balsamifera is an important medicinal plant, and pharmacological studies have focused on anti-microbial, anti-inflammatory effects, anti-tumor, wound healing, and anti-pathogenic activities, which confirm the traditional medicinal uses of the plant. In addition, several new pharmacological activities have been identified, such as antiviral (Xiong et al., 2022), anti-xanthine oxidase (Nguyen & Nguyen, 2012), and anti-obesity activities (Kubota et al., 2009).

4 Conclusion

In recent years, B. balsamifera has received more and more attention in many countries of Asia and extensive research has been conducted on its chemical constituents and pharmacological activities. Till now, 154 small molecular compounds including flavonoids, terpenoids, phenylpropanoids, steroids, etc. have been reported from B. balsamifera. The pharmacological investigations showed that B. balsamifera has various effects such as antioxidant, antibacterial, antitumor, hepatoprotective, anti-inflammatory, analgesic and wound healing promotion. This paper reviewed the chemical constituents and pharmacological activities of B. balsamifera for the further research, development, and utilization of B. balsamifera.

Acknowledgements

This work was financially supported by the Department of Science and Technology of Guizhou Province (Nos. QKHZC [2021] general 476, QKHZC [2023] general 426 and QKHPTRC [2018]5772-001), Guizhou Engineering Research Center of Industrial Key-technology for Dendrobium Nobile (QJJ [2022]048 and QJJ [2022]006).

• Practical Application: The review provides a comprehensive information for consumers and researchers to understand Sembung Chemical constituents and bioactivities.

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Publication Dates

• Publication in this collection
  17 Mar 2023
• Date of issue
  2023

History

• Received
  06 Jan 2023
• Accepted
  22 Jan 2023