Role of Acacia catechu and Scutellaria baicalensis in Enhancing Immune Function Following Influenza Vaccination of Healthy Adults: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial

Figures & data

Figure 1. Study design.

Table 1. Baseline demographic characteristics for participants in the intent-to-treat (ITT) population (n = 50).

Parameter	UP446 N (%)		Placebo N (%)		p-value
Gender					0.943
Female	17	(68.0)	16	(64.0)
Male	8	(32.0)	9	(36.0)
Age, Mean (SD)	25	52.1 (6.9)	25	53.8 (9.5)	0.203
Marital Status					0.873
Married or Common-law	16	(72.0)	19	(76.0)
Divorced or Separated	5	(20.0)	3	(12.0)
Single	3	(12.0)	3	(12.0)
Widow/Widower	1	(4.0)	0	0
Education level					0.149
High School graduate or GED	4	(16.0)	5	(20.0)
College diploma	9	(36.0)	10	(40.0)
University degree	11	(44.0)	7	(28.0)
Master’s degree or higher	1	(4.0)	2	(8.0)
Other	0	0	1	(4.0)
Employment					0.121
Full-time employment	19	(76.0)	11	(44.0)
Part-time employment	1	(4.0)	5	(20.0)
Unemployed	2	(8.0)	3	(12.0)
Other	3	(12.0)	6	(24.0)

All values presented are mean ± standard deviation (SD) unless otherwise stated.

Figure 2. Disposition of study participants.

Figure 3. Change in total (A) IgA, (B) IgG, and (C) IgM concentrations between UP446 and Placebo in the pre-vaccination period (baseline to Day 28), post-vaccination period (Day 28 to Day 56) and from baseline to end-of-study (EOS, Day 56) in the ITT population (n = 50). All values presented are mean ± standard deviation (SD). * indicates a significant within-group difference at the specific timepoint and ** indicates a significant difference between UP446 and Placebo.

Figure 4. Change in influenza A-specific (A) IgA, (B) IgG, and (C) IgM concentrations between UP446 and Placebo in the pre-vaccination period (baseline to Day 28), post-vaccination period (Day 28 to Day 56) and from baseline to end-of-study (EOS, Day 56) in the ITT population (n = 50). All values presented are mean ± standard deviation (SD). * indicates a significant within-group difference at the specific timepoint.

Figure 5. Change in influenza B-specific (A) IgA, (B) IgG, and (C) IgM concentrations between UP446 and Placebo in the pre-vaccination period (baseline to Day 28), post-vaccination period (Day 28 to Day 56) and from baseline to end-of-study (EOS, Day 56) in the ITT population (n = 50). All values presented are mean ± standard deviation (SD). * indicates a significant within-group difference at the specific timepoint.

Table 2. Immune cell phenotypes in blood of participants in the ITT population (n = 50).

Immune cell phenotype (%)	Study timepoint	UP446 Mean ± SD Within-group p-value	Placebo Mean ± SD Within-group p-value	UP446 vs. Placebo
Helper T Cells (CD3^+CD4^+)	Baseline	69.352 ± 9.326	68.729 ± 10.302	0.979
	Day 28	69.760 ± 8.249	68.379 ± 9.528	0.991
	Day 56	69.937 ± 7.763	69.172 ± 9.901	0.922
	Pre-Vaccination (Baseline to Day 28)	−0.164 ± 2.385 0.847	−0.049 ± 1.915 0.877	0.981
	Post-Vaccination (Day 28 to Day 56)	0.316 ± 2.072 0.353	0.793 ± 1.626 0.286	0.794
	Baseline to Day 56	0.134 ± 1.806 0.444	0.540 ± 2.079 0.286	0.933
Cytotoxic T Cells (CD3^+CD8^+)	Baseline	27.913 ± 7.742	30.046 ± 8.579	0.920
	Day 28	28.090 ± 7.351	29.954 ± 8.718	0.887
	Day 56	28.111 ± 7.227	29.286 ± 9.192	0.368
	Pre-Vaccination (Baseline to Day 28)	0.152 ± 2.223 0.812	−0.017 ± 1.757 0.963	0.869
	Post-Vaccination (Day 28 to Day 56)	−0.131 ± 1.998 0.590	−0.668 ± 1.412 0.146	0.494
	Baseline to Day 56	0.095 ± 2.185 0.754	−0.685 ± 2.003 0.133	0.432
T-Cell Receptor Gamma Delta Cells (TCR γδ^+)	Baseline	2.220 ± 2.045	1.874 ± 1.730	0.999
	Day 28	2.177 ± 2.285	1.755 ± 1.651	0.084
	Day 56	2.293 ± 2.158	1.852 ± 1.688	0.323
	Pre-Vaccination (Baseline to Day 28)	0.067 ± 0.419 0.556	−0.135 ± 0.497 0.175	0.164
	Post-Vaccination (Day 28 to Day 56)	0.044 ± 0.432 0.936	0.097 ± 0.511 0.351	0.721
	Baseline to Day 56	0.112 ± 0.444 0.498	−0.038 ± 0.331 0.672	0.440
NK Cells (CD3^−CD56^+)	Baseline	6.485 ± 3.733	10.039 ± 5.364	0.323
	Day 28	7.698 ± 3.605	9.874 ± 5.822	0.755
	Day 56	7.380 ± 3.176	9.291 ± 5.071	0.952
	Pre-Vaccination (Baseline to Day 28)	0.542 ± 2.565 0.389	0.223 ± 2.550 0.881	0.753
	Post-Vaccination (Day 28 to Day 56)	−0.152 ± 2.424 0.075	−0.583 ± 2.679 0.195	0.547
	Baseline to Day 56	−0.129 ± 2.278 0.974	−0.689 ± 1.897 0.025	0.906
Total Lymphocytes (CD45^+)	Baseline	35.808 ± 9.222	34.432 ± 8.056	0.828
	Day 28	33.616 ± 8.666	35.894 ± 8.145	0.026
	Day 56	35.909 ± 7.150	37.521 ± 7.926	0.077
	Pre-Vaccination (Baseline to Day 28)	−2.332 ± 4.755 0.067	1.350 ± 6.500 0.338	0.062
	Post-Vaccination (Day 28 to Day 56)	1.848 ± 5.735 0.075	1.627 ± 4.917 0.195	0.664
	Baseline to Day 56	−0.255 ± 6.024 0.974	2.977 ± 7.283 0.0521	0.136

All values presented are mean ± standard deviation (SD) unless otherwise stated.

Table 3. Serum concentrations of antioxidant and oxidative stress markers in participants in the ITT population (n = 50).

Marker (unit)	Study timepoint	UP446 Mean ± SD Within-group p-value	Placebo Mean ± SD Within-group p-value	UP446 vs. Placebo
Glutathione peroxidase (GSH-Px) (mU/mL)	Baseline	104.2 ± 29.9	108.1 ± 31.7	0.6285
	Day 28	118.4 ± 14.5	116.2 ± 11.4	0.4982
	Day 56	120.6 ± 14.5	117.9 ± 10.5	0.4451
	Pre-Vaccination (Baseline to Day 28)	14.2 ± 38.7 0.0270	8.1 ± 37.8 0.1847	0.5820
	Post-Vaccination (Day 28 to Day 56)	2.2 ± 25.2 0.7275	1.8 ± 19 0.7722	0.8327
	Baseline to Day 56	16.4 ± 27.1 0.0108	9.9 ± 27.8 0.1069	0.5408
Advanced glycation end-products (AGEs) (AU/mg)	Baseline	77 ± 7.9	76.9 ± 7.3	0.9828
	Day 28	83 ± 7.3	82 ± 6.9	0.6338
	Day 56	81.7 ± 5.2	81.7 ± 8.8	0.9764
	Pre-Vaccination (Baseline to Day 28)	6 ± 12.1 0.0053	5.1 ± 7.8 0.0132	0.7150
	Post-Vaccination (Day 28 to Day 56)	−1.3 ± 9 0.5503	−0.4 ± 10.2 0.8543	0.7448
	Baseline to Day 56	4.7 ± 8.7 0.0270	4.7 ± 11.1 0.0214	0.9818
Superoxide dismutase (SOD) (U/mL)	Baseline	1.2 ± 1	1.1 ± 0.2	0.9180
	Day 28	1.3 ± 1	1.3 ± 0.4	0.0170
	Day 56	1.2 ± 1.1	1.1 ± 0.2	0.5030
	Pre-Vaccination (Baseline to Day 28)	0.1 ± 0.3 0.3475	0.2 ± 0.4 0.0004	0.0392
	Post-Vaccination (Day 28 to Day 56)	−0.1 ± 0.3 0.4540	−0.2 ± 0.4 0.0067	0.2362
	Baseline to Day 56	0 ± 0.3 0.8482	0.1 ± 0.2 0.3995	0.5014

All values presented are mean ± standard deviation (SD) unless otherwise stated.

Table 4. Upper respiratory tract infection (URTI) symptom severity, well and sick days from the Modified Wisconsin Upper Respiratory Symptom Survey (WURSS)-24 in the ITT population (n = 50).

Variable	Study timepoint	UP446 Mean ± SD Median (Min to Max) Within-group p-value	Placebo Mean ± SD Median (Min to Max) Within-group p-value	UP446 vs. Placebo
Mean global severity index	Pre-Vaccination (Baseline to Day 28)	48.1 ± 135.2 0.0 (0.0 to 632.6)	4.0 ± 13.6 0.0 (0.0 to 63.8)	0.090
	Post-Vaccination (Day 28 to Day 56)	5.8 ± 21.0 0.0 (0.0 to 97.3)	11.4 ± 36.5 0.0 (0.0 to 172.7)	1.000
	Post-Vaccination vs. Pre-Vaccination	−29.8 ± 114.1 0.0 (-535.3 to 32.0) 0.113	7.2 ± 37.9 0.0 (-40.2 to 172.7) 1.000	0.659
Mean symptom severity scores	Pre-Vaccination (Baseline to Day 28)	35.1 ± 60.2 0.5 (0.0 to 237.9)	15.8 ± 21.3 0.0 (0.0 to 66.4)	0.670
	Post-Vaccination (Day 28 to Day 56)	20.4 ± 32.5 0.5 (0.0 to 99.0)	19.0 ± 27.8 0.0 (0.0 to 111.8)	1.000
	Post-Vaccination vs. Pre-Vaccination	−5.6 ± 52.9 0.0 (-193.2 to 99.0) 0.910	2.5 ± 16.7 0.0 (-14.8 to 59.2) 1.000	1.000
Number of well days	Pre-Vaccination (Baseline to Day 28)	26.7 ± 3.1 28.0 (14.9 to 28.0)	27.9 ± 0.3 28.0 (26.9 to 28.0)	0.666
	Post-Vaccination (Day 28 to Day 56)	27.8 ± 0.4 28.0 (27.0 to 28.0)	27.6 ± 1.3 28.0 (23.0 to 28.0)	1.000
	Post-Vaccination vs. Pre-Vaccination	0.6 ± 2.8 0.0 (-1.0 to 13.1) 0.278	−0.3 ± 1.4 0.0 (-5.0 to 1.1) 0.984	0.993
Number of sick days	Pre-Vaccination (Baseline to Day 28)	1.3 ± 3.1 0.0 (0.0 to 13.1)	0.1 ± 0.3 0.0 (0.0 to 1.1)	0.122
	Post-Vaccination (Day 28 to Day 56)	0.2 ± 0.4 0.0 (0.0 to 1.0)	0.4 ± 1.3 0.0 (0.0 to 5.0)	1.000
	Post-Vaccination vs. Pre-Vaccination	−0.6 ± 2.8 0.0 (-13.1 to 1.0) 0.278	0.3 ± 1.4 0.0 (-1.1 to 5.0) 0.984	0.993

All values presented are mean ± standard deviation (SD) unless otherwise stated.

Table 5. URTI symptom severity, well and sick days from the Modified WURSS-24 in the per protocol (PP) population (n = 46).

Variable	Study timepoint	UP446 Mean ± SD Median (Min to Max) Within-group p-value	Placebo Mean ± SD Median (Min to Max) Within-group p-value	UP446 vs. Placebo
Mean global severity index	Pre-Vaccination (Baseline to Day 28)	8.5 ± 28.9 0.0 (0.0 to 126.0)	4.2 ± 13.8 0.0 (0.0 to 63.8)	1.000
	Post-Vaccination (Day 28 to Day 56)	1.7 ± 6.8 0.0 (0.0 to 32.0)	11.4 ± 36.5 0.0 (0.0 to 172.7)	0.968
	Post-Vaccination vs. Pre-Vaccination	−6.8 ± 30.2 0.0 (-126.0 to 32.0) 0.996	7.2 ± 37.9 0.0 (-40.2 to 172.7) 0.992	0.949
Mean symptom severity scores	Pre-Vaccination (Baseline to Day 28)	16.3 ± 27.4 0.2 (0.0 to 88.9)	16.5 ± 21.5 1.5 (0.0 to 66.4)	1.000
	Post-Vaccination (Day 28 to Day 56)	19.3 ± 32.8 0.2 (0.0 to 99.0)	19.0 ± 27.8 0.0 (0.0 to 111.8)	1.000
	Post-Vaccination vs. Pre-Vaccination	3.0 ± 34.3 0.0 (-88.9 to 99.0) 1.000	2.5 ± 16.7 0.0 (-14.8 to 59.2) 1.000	1.000
Number of well days	Pre-Vaccination (Baseline to Day 28)	27.8 ± 0.6 28.0 (26.0 to 28.0)	27.9 ± 0.3 28.0 (26.9 to 28.0)	0.998
	Post-Vaccination (Day 28 to Day 56)	27.8 ± 0.4 28.0 (27.0 to 28.0)	27.6 ± 1.3 28.0 (23.0 to 28.0)	0.975
	Post-Vaccination vs. Pre-Vaccination	0.0 ± 0.5 0.0 (-1.0 to 1.0) 1.000	−0.3 ± 1.4 0.0 (-5.0 to 1.1) 0.889	0.993
Number of sick days	Pre-Vaccination (Baseline to Day 28)	0.2 ± 0.6 0.0 (0.0 to 2.0)	0.1 ± 0.3 0.0 (0.0 to 1.1)	0.998
	Post-Vaccination (Day 28 to Day 56)	0.2 ± 0.4 0.0 (0.0 to 1.0)	0.4 ± 1.3 0.0 (0.0 to 5.0)	0.975
	Post-Vaccination vs. Pre-Vaccination	−0.0 ± 0.5 0.0 (-1.0 to 1.0) 1.000	0.3 ± 1.4 0.0 (-1.1 to 5.0) 0.889	0.993

All values presented are mean ± standard deviation (SD) unless otherwise stated.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.